Review Article Influence of Physical Activity and Nutrition on Obesity-Related Immune Function

13 Pages·2015·1.29 MB·English

HindawiPublishingCorporation
TheScientificWorldJournal
Volume2013,ArticleID752071,12pages
http://dx.doi.org/10.1155/2013/752071
Review Article
Influence of Physical Activity and Nutrition on
Obesity-Related Immune Function
Chun-JungHuang,1MichaelC.Zourdos,1EdwardJo,2,3andMichaelJ.Ormsbee3
1DepartmentofExerciseScienceandHealthPromotion,FloridaAtlanticUniversity,777GladesRoad,FH11A-126B,
BocaRaton,FL33431,USA
2DepartmentofKinesiologyandHealthPromotion,CaliforniaStatePolytechnicUniversity,Pomona,Pomona,CA,USA
3DepartmentofNutrition,FoodandExerciseSciences,TheFloridaStateUniversity,Tallahassee,FL,USA
CorrespondenceshouldbeaddressedtoChun-JungHuang;[email protected]
Received31August2013;Accepted19September2013
AcademicEditors:F.D’AcquistoandA.A.Manfredi
Copyright©2013Chun-JungHuangetal. This is an open access article distributed under the Creative Commons Attribution
License,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperly
cited.
Researchexaminingimmunefunctionduringobesitysuggeststhatexcessiveadiposityislinkedtoimpairedimmuneresponses
leadingtopathology.Thedeleteriouseffectsofobesityonimmunityhavebeenassociatedwiththesystemicproinflammatoryprofile
generatedbythesecretorymoleculesderivedfromadiposecells.Theseincludeinflammatorypeptides,suchasTNF-𝛼,CRP,and
IL-6.Consequently,obesityisnowcharacterizedasastateofchroniclow-gradesystemicinflammation,aconditionconsiderably
linkedtothedevelopmentofcomorbidity.Giventhecriticalroleofadiposetissueintheinflammatoryprocess,especiallyinobese
individuals, it becomes an important clinical objective to identify lifestyle factors that may affect the obesity-immune system
relationship.Forinstance,stress,physicalactivity,andnutritionhaveeachshowntobeasignificantlifestylefactorinfluencing
theinflammatoryprofileassociatedwiththestateofobesity.Therefore,thepurposeofthisreviewistocomprehensivelyevaluate
theimpactoflifestylefactors,inparticularpsychologicalstress,physicalactivity,andnutrition,onobesity-relatedimmunefunction
withspecificfocusoninflammation.
1.Introduction immune functions [6–8]. The confirmed presence of secre-
torymoleculesderivedfromadipocytes,suchasproinflam-
The global epidemic of obesity is irrefutably a major public matorycytokines(e.g.,tumornecrosisfactor-alpha[TNF-𝛼]
health issue largely because of its comorbidities, namely, and interleukin-6 [IL-6]), constitutes the unique endocrine
cardiovascular disease, type II diabetes, and cancer. Never- functionofadiposeandprovidesvaluablepathophysiological
theless,theprevalenceofobesityhasdrasticallyescalatedby insight regarding obesity and its comorbidities [7]. During
nearly57%overtheprevioustwodecades[1,2].TheNational unhealthy weight gain, the influx and storage of excess
HealthandNutritionExaminationSurvey(NHANES2009- lipids in adipocytes perturbs normal cell function, which
2010)reportedthat36%ofUSadultsarecurrentlyclassified consequentlyinducestheoverexpressionandhyper-secretion
asobese (BMI ≥30kg/m2), while16% representincidences of inflammatory peptides into circulation [9]. As a result,
of severe cases (BMI ≥ 35kg/m2) [2]. Based on projections obesity is now recognized as a state of low-grade systemic
derivedfrompreviousNHANESdata,86%ofU.Sadultswill inflammation characterized by high circulating levels of
beoverweight(BMI≥25kg/m2)orobese(obesityaccounting inflammatorymolecules,suchasTNF-𝛼,IL-6,andC-reactive
for 51.1%) by 2030 if this epidemiological trend remains protein (CRP) [10, 11]. Due to the deleterious effects of
unresolved[3–5]. systemicinflammationonmultipleorgantissues,unhealthy
Overthepasttwodecades,adiposetissuehasbeenestab- weightgainisassociatedwithhighriskofdevelopingserious
lished as a multifunctional organ playing a critical role healthconditions,suchastypeIIdiabetesandcardiovascular
not only in lipid/energy storage but also in endocrine and disease [7, 12]. Given the involvement of adipose tissue in
2 TheScientificWorldJournal
the inflammatory process, especially in excessive states, it In addition, our laboratory recently found that following a
becomes an important clinical objective to identify lifestyle combinedphysicalandpsychologicalstress,NEarea-under-
factorsthatmayaffecttheobesity-immunesystemdynamic. the-curve(AUC)wasnegativelycorrelatedwiththepercent-
For instance, stress, physical activity, and nutrition have age of CD19+ B cells, and heart rate (HR) was negatively
eachshowntobesignificantlifestylefactorsinfluencingthe associatedwiththepercentagechangeintheCD4/CD8ratio
inflammatoryprofileassociatedwiththestateofobesity[13– [35]. These elevations in NE and HR simultaneously in
15].Ofparticularinterest,itiswelldocumentedthatchronic response to the dual challenge suggest greater sympathetic
inflammationisalsohighlycorrelatedtonutritionalfactors activationthat,inturn,couldpossiblyexplainthealteration
in the distribution of lymphocyte subsets, resulting in inef-
suchasthetypeandamountofcarbohydrates,proteinsand
fectivecell-mediatedimmuneresponses[36,37].Therefore,
fats that are consumed in the diet [16–18]. Therefore, the
these findings indicate that acute stress enhances innate
purpose of this review is to comprehensively evaluate the
immunity and possibly suppresses adaptive immunity, and
impactoflifestylefactors,inparticularpsychologicalstress,
thesealterationscanbelikelyenhancedathigherintensities
physical activity, and nutrition, on obesity-related immune
ofphysicalstress.Theappropriateredistributionofimmune
functionwithspecialfocusoninflammation.
cellsinresponsetoacutestressorsisimperativetoaneffective
and efficient immune response in preparation for potential
2.StressandObesity invaders and injury [26, 38]. However, when exposed to
chronic stress, immunoprotection can be suppressed by
Stressinthebodyisestablishedthroughsometypeofstres- reducing immune cell number, function (cytotoxicity), and
sor(s), either physical or psychological. When stimulated, proliferation, thereby promoting susceptibility to diseases
the human body responds in a complex manner, incorpo- [39,40].
ratingtheintertwinedactivityoftheendocrineandnervous Obesityisconsideredachronicinflammatorycondition
systems(hypothalamic-pituitary-adrenal[HPA]andsympa- that enhances the risk of numerous inflammatory diseases,
thoadrenal[SA]axes).Stresshormonessuchascortisolfrom includingdiabetesandcardiovasculardisease(CVD).These
HPAaxisandcatecholamines(epinephrine(EPI)andnore- obesity-attributableillnesseshavebeendiscoveredtohavea
pinephrine(NE))fromtheSAaxishavebeenshowntoalter strongassociationwithinflammatoryparametersinplasma
immunecellresponses,andthisimportantimmunesystem such as proinflammatory cytokines (TNF-𝛼 and IL-6) [41,
responsecoordinatesanumberofthebody’sadaptationsto 42]. In addition to plasma inflammatory mediators, the
thestressor.Notably,elevationsinstresshormones(cortisol circulating mononuclear cells in obese individuals may be
andcatecholamines)arethoughttohavedetrimentaleffects morereadilystimulatedtoproduceinflammatorycytokines
on the immune system, leading to an imbalance between [43]. Interestingly, along with physical illnesses, obesity is
innate(immediateantigen-nonspecificdefense)andadaptive associatedwithjob-associatedstressandpsychosocialdisor-
immunity (specific response to a particular foreign antigen derssuchasdepressionandchronicanxiety[44–46].These
creatingimmunologicalmemory)viathereleaseofimmune stress-relateddisordershavebeenfoundtoleadtoincreased
mediatorssuchascytokines[19].Inresponsetoacutestress, riskofCVDandmortalityinobesepatients[47].
the innate immune promptly prepares to provide immune Chronicstresshasbeenshowntobeassociatedwithdis-
protectionfollowedbyadaptiveimmunitywhenexposedto turbancesoftheHAandSAaxesandislinkedtoabdominal
repeatedorprolongedstress,whereaschronicstresscansup- adiposity [48]. In response to acute stress, elevated cortisol
presstheseimmunedefenses.Thisstress-immuneinteraction levels are associated with high central adiposity [49–51].
isanimportantantiviraldefenseandfosterstheelimination Furthermore, studies have demonstrated an increase in SA
ofinvadingmicroorganisms[20,21]. axis reactivity in obesity patients [52–54]. This occurrence
Research has shown that stress induces changes in seemstobepivotaltounderstandhowstressmayupregulate
immune cell distribution [22–25], which ensures that the theinflammatoryconditionsinobeseindividuals.Recently,
body’s immune response is efficient or elicits an effective studieshaveshownthatobesesubjectsexhibithigherproin-
immunoprotection. An appropriate distribution of periph- flammatorycytokineproductionsuchasIL-6inplasmaand
eral immune cells provides for the performance of surveil- ex vivo compared with normal-weight subjects in response
lance and effector functions of the immune system [26]. toacutementalstress[50,55].Althoughchronicallyelevated
The release of catecholamines and cortisol in response to cortisolisthoughttohavedeleteriouseffectsontheimmune
stressors (physical or psychological) can mediate changes system, a suppressive effect of immune regulation has been
in the immune cell distribution [27, 28]. In response to showninresponsetoacutestressors[56].Importantly,Wirtz
acutestress,immuneresponseisprimarilyregulatedbycat- et al. [57] have revealed that individuals with higher body
echolamines[24].Thisisfurthersupportedbyotherstudies mass index demonstrated lower glucocorticoid sensitivity,
demonstratingtransientimmunecellredistributionviabeta- resulting in a diminished ability to inhibit production of
adrenergic activation following acute mental stress [23, 27, TNF-𝛼followingacutementalstress.
29, 30]. Specifically in response to exercise, monocytes and Inaddition,𝛽-adrenergicreceptorshavebeenshownto
NK cells (innate immunity) exhibit the greatest fluctuation mediate catecholamine-induced decreases in proinflamma-
followedbyCD3+TcellsandCD19+Bcells(adaptiveimmu- tory cytokines [58, 59]. Stress has been demonstrated to
nity) [31–33]. These alterations in immune cells have been downregulatebeta-adrenergicreceptorexpressionandfunc-
showntocorrespondwiththereleaseofcatecholamines[34]. tionsonmonocytesandNKcells,resultingintheelevation
TheScientificWorldJournal 3
of TNF-𝛼 and IL-6 [46]. These are key proinflammatory incidence of infection compared to inactive and sedentary
cytokines involved in CVD, chronic anxiety, and depres- individuals [75, 76], suggesting that physical activity may
sion [60]. Furthermore,previous studies demonstrated that improve the immune response. Moreover, these benefits to
increasedtension-anxiety,asubscaleoftheProfileofMood immune function in relation to regular exercise include
States (POMS), is correlated with the downregulation of 𝛽- decreased levels of proinflammatory cytokines TNF-𝛼 [77],
adrenergic receptors [61]. Individuals with high life stress IL-6 [78], and CRP [79] along with an increase in the anti-
and hostility have less lymphocyte 𝛽-adrenergic sensitivity inflammatory marker (IL-10) [78]. Additionally, exercise is
[62].Takentogether,thesefindingssuggestthatobesitycould associatedwithdecreasedlevelsofdepression[80].Tofully
diminish the inhibitory effect of 𝛽-adrenergic receptors in
comprehend the positive benefits of exercise to immune
response to acute stress, resulting in a greater release of
function it is necessary to examine the stress and recovery
proinflammatory cytokines [50, 55]. Thus far, it has been
response to exercise. Additional insight into how exercise
discoveredthatobeseindividualshavereduced𝛽-adrenergic
affectsacuteandchronicinflammationisnecessarytounder-
receptor density [63] and higher plasma NE and EPI con-
stand the importance of exercise as an antagonist to the
centrations [64]. Hence, the investigation of mechanisms
currentobesityepidemic.
of 𝛽-adrenergic receptor regulation to stress may provide
insightintotheroleofpsychoneuroimmunologicalprocesses
inobesepopulations’healthanddisease. 3.1.ExerciseandtheStressResponse. Intenseexercisetraining
places a stimulus on the body often resulting in myofiber
Althoughtheunderlyingmechanismscontributingtothe
damage, muscle soreness, and edema [81]. This damaging
relationship of the stress response, obesity, and proinflam-
effectparticularlyoccursinnovicetraineeswhoarestressed
matorycytokinesremaintobedetermined,elevatedlevelsof
by an unfamiliar stimulus. This initial fatigue in response
leptinhaverecentlybeenimplicatedasacontributingfactor
to a new stimulus is described in Hans Seyle’s landmark
thatlinksacutestresstoinflammation.Leptin,anadipocyte-
work, the general adaptations syndrome (GAS) [74], as the
derived hormone, plays an important role in metabolism,
“alarmreactionstage.”Followingtheinitialalarmresponse,
adiposity,andvascularinflammationandhasbeenimplicated
theGASexplainsthatoncerecoverytakesplace,anindividual
in the development of coronary heart disease [65]. In vitro
enters the stage of resistance, indicating the capability of
stimulation of cultured human endothelial cells with leptin
undertakingfurtherstress.Theonsetofthestageofresistance
has induced an increased accumulation of levels of proin-
signifies the adaptation to the initial stress realized in the
flammatorymediator(e.g.,monocytechemotacticprotein-1)
alarm stage. This concept of initial fatigue and recovery is
via activation of nuclear factor-kappa B [66]. Interestingly,
similar to the repeated bout effect (RBE), which states that
recent research has shown that people who undergo acute
performingthesameexercisestimuluswithin6monthsofthe
mentalstressdemonstrateincreasesinleptinlevels,andthese
initialboutresultsinanattenuatedlevelofmyofiberdamage
increases are positively correlated with waist circumference
[81].Consequently,theincurredadaptationisspecifictothe
[67, 68]. Brydon et al. [68] also showed that a positivecor-
task performed in the initial exercise bout. This concept of
relation between basal circulating leptin and IL-6 exists
specificity is otherwise known as the specific adaptations
in response to mental stress. These findings suggest that
to imposed demands (SAID) principle, which states that
leptin may partially contribute to inflammatory response
individualsadapttothespecificstressorplaceduponthemto
followingacutestress.Futureinvestigationshouldattemptto
becomemorefit forlivingconditions[82]. Althoughinitial
understandthemechanismscontributingtotherelationship
fatigue leads to long-term adaptation without programmed
betweenobesityandproinflammatoryreactivitytostress.In
restandvariationtoexercise-trainingvolumeandintensity,
turn, an understanding of how the mind and body interact
tissue repair may not fully transpire and overtraining syn-
and impact health can directly influence how we develop
drome may develop [83]. Moreover, lack of ample recovery
targetedtreatments,suchasexercise-trainingandweightloss
fortissuerepairmayresultinchronicinflammationandcen-
programs,astherapeuticinterventionsforobesity-associated
tralfatiguepotentiallyhavingdeleteriouseffectsonexercise
cardiovascular, chronic infectious, and inflammatory neu-
performance.Furthermore,astateofchronicinflammation,
ropsychiatricdiseases.
which impairs immune function, may contribute to an
increasedprobabilityofobesity,CVD,anddiabetes.
3.PhysicalActivityandImmuneFunction
3.2. Acute and Chronic Inflammation. When dissecting the
Physicalactivityhaslongbeenassociatedwithimprovements subsequenteffectsoftheinflammatoryresponse,itisneces-
in aerobic capacity [69], strength [70], muscle growth [71], sarytounderstandthatinflammationcanbebothacuteand
and body composition [70]. However, it is now widely chronicinnature[84].Acuteinflammationisanimmediate
accepted that chronic physical activity enhances immune response to stress and may not necessarily be indicative of
function and attenuates the likelihood of chronic disease, long-term adaptations. To illustrate, acute stress hormone
such as CVD, diabetes, and obesity [72, 73]. Initially, unac- response, such as cortisol, has increased significantly in
customed exercise places a stressor on the body resulting response to high-volume resistance training [85]. However,
in fatigue [74]; however, once the recovery process occurs, long-term exercise training of two years in length has
beneficial adaptations are the result. In fact, fit individuals resulted in decreased resting cortisol concentrations [86].
(thosewhopartakeinregularphysicalactivity)havealower Thus, chronic exercise training appears to reduce resting
4 TheScientificWorldJournal
cortisollevels.Therefore,acuteelevationsinmarkersofstress 3.5.Summary. Obesityisachronicinflammatorycondition,
signify an immediate stress response; however, long-term whichenhancestheriskofCVDandisassociatedwithvari-
adaptations to physical activity appear to favor parasympa- ousinflammatorycytokines(TNF-𝛼andIL-6).Whenintro-
theticdominance. ducedasanewstressor,exerciseacutelyincreasescatabolic
responses [85], resulting in muscle fatigue [74]. However,
researchindicatesthatregularparticipationinexerciseleads
3.3. Exercise and Acute Inflammation. A typical acute
to decreased systemic inflammation [93]. Indeed, Colbert
response to an infection, stressor, or immune system stim-
et al. [72] related higher levels of physical activity to lower
ulatorlipopolysaccharide(LPS)istheelevationoftheproin-
levels of IL-6 and CRP. Furthermore, exercise is beneficial
flammatorycytokineTNF-𝛼[87].Inratsthatwereexercised
during the aging process to decrease catabolic hormone
to exhaustion (an average of 102 minutes), an attenuated
responses[100].Consequently,exerciseseemstoprovidesig-
TNF-𝛼 response was measured compared to the response
nificantbenefitsthatenhanceimmunefunctionanddecrease
in nonexercised rats when administered with LPS for up
inflammation.Thus,exerciseisrecommendedasaneffective
to 6 hours [87]. In agreement, in human data, healthy
strategytopositivelyalterobesity-relatedimmunefunction.
men who performed aerobic exercise to exhaustion prior
to the infusion of LPS exhibited lower levels of TNF-𝛼
comparedtoanon-exercisinggroup[77].Likewise,Nosaka 4.NutritionandInflammation
and Clarkson [88] reported no increase in plasma levels
of TNF-𝛼 following a bout of damaging resistance training 4.1.Macronutrients:QualityandQuantity
of the elbow flexors. Interestingly, TNF-𝛼 levels have been
reportedtobesignificantlyelevatedinobesepopulations[89, 4.1.1.EnergyContent. Chronicinflammationisinfluencedby
90].Indeed,TNF-𝛼hasbeenestablishedtobeassociatedwith energybalance.Acuteoverconsumptionofenergyhasconsis-
insulin resistance, leading to obesity [91]. Ultimately, both tentlyresultedinincreasesinmarkersofinflammation[101].
aerobicandresistanceexercisemaybeeffectiveinattenuating Theseincreasesoccurwithorwithoutweightgain,suggesting
acuteinflammatoryresponses,whichmighthavesignificant thatchronicinflammationinoverweightorobeseindividuals
implicationstopreventingobesity. maybestronglyinfluencedbycaloricloadandnotnecessarily
theprimaryresultofincreasedadiposity.Thismayalsohelp
to explain the prevalence of chronic disease in the Western
3.4. Exercise and Chronic Inflammation. Numerous studies
world where diets often include calorie-dense foods (e.g.,
have been conducted on the relationship between exercise
“fastfood”).Conversely,caloricrestrictionand/orfastingcan
and concentrations of CRP [79, 92, 93]. These studies all
alsoresultinincreasesininflammation[102].Thesefindings
demonstrate an inverse relationship between CRP concen-
suggestmaintenanceofenergybalanceasanimportantfactor
trations and physical activity [92]. Further, physical fitness
in the prevention of systemic inflammation. Interestingly,
measured by maximal oxygen consumption (VO2 max) is outsideofenergybalance,thetypeofmacronutrientsthatwe
alsoinverselyrelatedtoCRPconcentrations[94].Dataalso
consumealsoplaysapivotalroleinwhole-bodyinflamma-
indicates that active older men (i.e., exercising 4 days/wk)
tion.
have lower levels of IL-6 and greater levels of IL-10 when
compared to older men who perform a low amount of
physicalactivity(i.e.,notactivemostdaysoftheweek)[78]. 4.1.2. Carbohydrates. Carbohydrates (CHO) can dramati-
Moreover, multiple studies show that lifestyle interven- callyinfluencewhole-bodyinflammation.Inaddition,there
tions with exercise impact the inflammatory response [95– are many factors that affect the inflammatory potential of
98]. Balagopal et al. [95] reported that obese adolescents CHO intake including glycemic index (GI), glycemic load
whounderwenta3-monthlifestyleinterventionofenhanced (GL),anddietaryfiber.ThedegreetowhichaCHOincreases
physicalactivityandnutritionhabitshaddecreasedbodyfat the blood sugar response (high-GI equals greater increases
percentage, insulin resistance, CRP, and IL-6. Additionally, in blood sugar) will influence the inflammatory response.
ninemonthsofendurancetrainingin14individualsprepar- In fact, GI has consistently shown a positive correlation
ingforamarathonresultedindecreasedlevelsofCRP[92]. with biomarkers of whole-body inflammation. Specifically,
Likewise, an exercise intervention of 3 years, which gave markersofinflammationincreaseacutelyfollowingahighGI
detailed advice in regard to physical activity, in 60 obese meal[103].Ofnote,markersofinflammationeitherdecline
women resulted in weight loss along with decreased levels or remain unchanged following low-GI meals [104]. This
ofTNF-𝛼[99].Infact,an8-weekexercise-trainingprogram discrepancymaybeafunctionofGL,theproductofdietary
consistingof4days/wkofcyclingbetween40and50%VO2 GI,andquantityofCHOactuallyeaten,asconsumptionof
peak did not affect insulin sensitivity or CRP levels despite alargequantityoflow-GIfoodhasbeenshowntoincrease
improvements in aerobic fitness and endothelial function markers of inflammation to a similar degree as to the con-
[96]. One possible explanation for these conflicting results sumptionofasmallquantityofhigh-GIfood[105].However,
isthattheinterventiondurationof8weekswastooshortto data on the relationship between GL and inflammation are
elicitchangesininsulinsensitivityandCRPlevels.Ultimately, conflicting. Although some studies have shown a positive
itseemsthatlong-termexerciseinterventions(greaterthan8 correlationbetweendietaryGLandmarkersofinflammation
weeks)areeffectiveinreducetheinflammationresponseand (i.e., C-reactive protein, CRP) [106, 107], others have failed
improvephysicalfitness. toreportasignificantassociation[108].Thisdivergencemay
TheScientificWorldJournal 5
be due to differences in energy content of the diets in GL noninflammatory effects have been reported with omega-6
studies, which, as discussed above, has been shown to have consumption [122]. Indeed, the effectiveness of PUFAs in
a strong relationship with inflammation [109]. Many GL reducing markers of inflammation may lie in the ratio
studiescomparevaryingdietaryCHOamountswhilesimul- between omega-3 and omega-6 PUFAs. It has also been
taneouslylimitingcaloriesto encourageweight loss. There- suggested that a higher ratio of omega-3 to omega-6 PFAs
fore,thesealterationsmaygoagainsteachotherandpossibly increasestheanti-inflammatorypotentialofthesefats[123].
explaintheconfoundingresults. MUFAsalsoappeartobeanti-inflammatoryasseveralstudies
Increased consumption of refined carbohydrates in the [124, 125], but not all [118], have reported an inverse rela-
modern diet has not only led to increased consumption of tionship between MUFA levels and inflammatory markers.
high-GIdietsbutalsoreducedintakeofdietaryfiber.Thislow Strongerevidenceforthisinverserelationshipisfoundspecif-
fiberintakemayexplaintheincreasedprevalenceofchronic ically between olive oil consumption, which contains high
inflammationanddiseaseasnumerousstudieshavereported levelsofMUFAs,andsystemicinflammatorymarkers[126].
an inverse relationship between fiber intake and CRP [110].
Of interest, the anti-inflammatory effects of fiber appear to
4.1.4.Protein. Theeffectsofproteinsoninflammationseem
holdtrueforbothdietaryfiberandfibersupplements[111].
to vary depending on the source of the protein. Red meat
Moreover,thisrelationshipmayalsoholdtrueforinsoluble
istypicallyconsideredasproinflammatory.Thisislikelydue
fibers, which have been shown to positively affect immune
totheassociationbetweenhighdietaryredmeatintakeand
function[112].Dietaryfibermayalsoinfluenceinflammation
bothcoronaryheartdisease[127]andtypeIIdiabetes[128].
through its mediating effects on glycemia. In one lifestyle
However,evidencefromstudiesonleanredmeathasfailed
intervention study on a representative sample of Italian
toshowanyincreaseinmarkersofinflammation[129].This
adults, blood CRP concentrations were lowered along with
suggeststhatthequalityofthemeatmaybemoreindicative
fasting blood glucose in response to increased fiber intake,
independentofweightloss[113].Thus,perhapsbymediating ofitsinflammatorypotential.Indeed,consumingprocessed
theabsorptionofnutrientsandmodulatingchangesinblood meat(e.g.,bacon,hamburger,andsausage)seemstoincrease
sugar,fibereffectivelyreducesinflammation. theriskoftypeIIdiabetes,whichisassociatedwithincreased
whole-bodyinflammation[130].
Inflammation from protein ingestion may also vary
4.1.3.Fats. Theinflammatorypotentialoffatisafunctionof
between meat-based, plant-based, and milk-based proteins.
thetypeoffatbeingconsumed.Numerousstudieshaveimpli-
InastudyfromDenmark,obeseparticipantswerefedasingle
cated saturated fats (SFAs) as inflammatory agents. SFAs,
high-fat meal containing 4 different sources of protein: fish
whicharecommonlyfoundinprocessedmeat,refinedgrain,
(cod),wheyisolate,gluten,orcasein.Serumlevelsofinflam-
and/orfriedfoods,havebeenshowntoincreasemarkersof
matorycytokinesweremonitoredinthe4hoursfollowingthe
inflammation such as CRP, IL-6, and E-selectin, a vascular
adhesionmolecule[114].AstrongcorrelationbetweenSFAs meal.Codproteinandglutenresultedinabluntedincreasein
andCRPcanbefoundintheNationalHealthandNutrition markersofinflammationversusthewheymealbutwerenot
Education Survey (NHANES 99-00) [115]. Furthermore, different from the casein meal [131]. Therefore, consuming
Aryaetal.[116]reportedthatamongotherdietarynutrients, cod protein and/or plant-based protein may be beneficial
SFAlevelswerethemostimportantpredictorofCRPlevels. for whole-body inflammation relative to some milk-based
However,itshouldbenotedthatsomestudieshavefailedto proteins(whey).Evidencealsoexiststosupporttheuseofsoy
showacorrelation[117]or,insomecases,haveevenshowna proteintobluntinflammation.Infact,reductionsinmarkers
slightnegativecorrelationbetweenSFAandCRPlevels[118]. ofinflammationhavebeenshownwithconsumptionofsoy
Thisdiscrepancymaybeduetothepopulationstudiedand [132], soybean oil [133], and soy nuts [134]. More data is
confounding variables such as other nutrients included in needed,however,beforeadefinitiveconclusioncanbemade
thediet,physicalactivity,andthepopulationstudied.Trans forwhichtypesofproteinsmayworkbesttoreducewhole-
fats (TFA), fatty acids containing one double bond created bodyinflammation.
viahydrogenationofvegetableoils,whicharefoundinfoods
such as butter, margarine, milk fat, and fried foods, may
alsoincreasemarkersofinflammation.IntheNurses’Health 4.2.Micronutrients/Antioxidants
Study,astrongcorrelationwasshownbetweenTFAlevelsand
4.2.1. Flavonoids. Flavonoids, naturally occurring antioxi-
inflammatorybiomarkersofCRP,IL-6,andE-selectin[119].
dant, commonly found in foods such as onions, apples,
ThismayexplainthestrongconnectionbetweenserumTFA
grapes, berries, and cocoa, are anti-inflammatory agents.
levelsandcoronaryheartdisease[120].
Commonflavonoidssuchasquercetin,kaempferol,malvidin,
Conversely, monounsaturated fatty acids (MUFAs) and
peonidin,daidzein,andgenisteinhavebeenreportedtohave
polyunsaturated fatty acids (PUFAs) have an inverse rela-
aninverserelationshipwithCRP[135].
tionshipwiththeinflammatorybiomarkers.Levelsofcertain
PUFAs such as omega-3 fatty acids, common in cold-water
fish, are consistently found to have an inverse relationship 4.2.2.Carotenoids. Carotenoidsarethenaturalpigmentsthat
with IL-6 [121]. The effects of other common PUFAs such givemanyfruitsandvegetablestheirdistinctivebrightcolors.
as omega-6 fatty acids are less clear. Inflammatory and These are found in abundance in oranges, sweet potatoes,
6 TheScientificWorldJournal
kale,andspinach.Carotenoidssuchasalpha-carotene,beta- the potential of anthcyanins to inhibit cancer formation in
carotene,andluteinseemtohaveanti-inflammatorypoten- rodents [147]. This finding could be the result of reported
tial.Infact,participantsofonestudywiththehighestserum anti-inflammatorypropertiesofanthocyanins.Arecentstudy
levelsofalpha-caroteneweresignificantlylesslikelytohave on participants with high blood cholesterol levels reported
highlevelsofIL-6.Interestingly,theoppositewasalsofound thatconsumptionofananthocyaninsupplementtwicedaily
tobetruewherelowlevelsofvariouscarotenoidsintheblood for24weeksresultedinreductionsinCRPandothermarkers
wereassociatedwithincreasedlevelsofIL-6[136].Further- ofsystemicinflammation[148].
more,anotherstudyreportedapotentiallyprotectiveeffectof Bromelain is a proteolytic enzyme found primarily in
luteinandlycopeneagainstatherosclerosis,whichtheauthors pineapples. Among many other therapeutic benefits (e.g.,
report to be likely a result of a reduction in inflammatory improved endothelial function, enhanced absorption of
markers[137]. antibioticdrugs,andinhibitionoftumorcellgrowth),brome-
lain is an effective anti-inflammatory agent [149]. These
4.2.3. Magnesium. Magnesium, found typically in whole anti-inflammatory properties have been observed in vitro
grain,greenleafyvegetables,nuts,andlegumes,maybeone viaitsmodulatingeffectoncertaininflammatorycytokines
ofthemosteffectiveagentsforcombattingchronicinflamma- [150]. The benefits are also apparent in clinical trials which
tion.Numerousstudieshavereportedtheinverserelationship report the effectiveness of bromelain for treating certain
betweenmagnesiumintakeandCRPandIL-6[119,138],in inflammation-deriveddiseases/conditions(e.g.,osteoarthri-
somecasesinadose-dependentmanner[138]. tis)[151].
4.2.4. Vitamins. Vitamins, found commonly in fruits and 4.4.Beverages
vegetables, are essentialto immunefunctionandare thusa
necessaryimpedimenttoexcessiveinflammation.Numerous 4.4.1. Tea/Coffee. Tea consumption is associated with
vitamins such as vitamins C, E, A, B6, and riboflavin each reduced markers of inflammation. In fact, after 6 weeks of
havebeenassociatedwithreducedcytokineproduction(e.g., blackteaconsumptioninhealthymen,therewasareduction
IL-6)[139]. in CRP and platelet aggregation [152]. Green tea may have
similarpropertiesasithasbeenindicatedtobeaneffective
antioxidantinvitro[153].However,theeffectivenessofgreen
4.3.WholeUnprocessedFoods
teaatreducingmarkersofinflammationlikeCRPinclinical
trials is less clear. Studies examining 1-month to green tea
4.3.1. Fish. In general, consumption of fish has been linked
consumptiononhealthymales[154]andmalesmokers[155]
to various health benefits, particularly heart health [140].
havefailedtoreportaneffectonCRPlevels.
Some of these health benefits may be due to reductions in
markers of inflammation [141]. This seems likely as certain The effects of coffee consumption on inflammation are
fish, particularly cold-water fish like salmon and mackerel, equivocal. Some studies have reported anti-inflammatory
containhighlevelsofPUFAslikeomega-3fattyacids,which effects[156],whileothershavereportednoeffectsatall[157].
as discussed above, likely have anti-inflammatory effects. Thiscouldbeduetogeneticfactorsasarecentstudyrevealed
Indeed, the anti-inflammatory nature of fish seems to be a a genetic polymorphism affecting one’s responsiveness to
direct result of PUFA content as numerous studies on fish caffeine[158].Becausecaffeinemayhaveanti-inflammatory
oil supplements (high in omega-3 PUFAs) have reported properties [159], the effectiveness of coffee as an anti-
reductions in markers of whole-body inflammation [142, inflammatoryagentmaybemediatedbyone’sresponsiveness
143]. In agreement, using salmon fed 3 different diets to tocaffeine.Whilespeculative,theimpactofphysicalactivity
manipulate the omega-3 fatty acid content of the fish, it and other lifestyle factors likely plays a critical role in the
was found that only the participants consuming salmon overallanti-inflammatoryresponsetothesenutrients.
containingthehighestlevelsofomega-3ssawreductionsin
IL-6[144].
4.4.2. Alcohol. The effectiveness of alcohol at reducing or
preventing inflammation seems to depend on the amount
4.3.2. Fruits and Vegetables. A large body of research exists consumed.Whileexcessiveconsumptionand/orbingedrink-
documenting the many health benefits of consuming fruits ingisknowntohavemanyadversehealthoutcomesincluding
andvegetables[140].Moreover,theanti-inflammatoryeffects increasedinflammation[160],moderateintake(e.g.,∼150mL
ofconsumingfruitandvegetablesarewelldocumented[145, of wine per day) of alcohol seems to reduce markers of
146].Thisisnosurpriseconsideringthatfruitsandvegetables inflammation in various populations [161]. The degree to
contain high concentrations of dietary fiber, flavonoids, whichthesemarkersarereducedmaydependonthesource
carotenoids, and vitamins, which have all been associated of alcohol. Red wine, for example, has consistently been
with reductions in markers of inflammation, as discussed reported to have anti-inflammatory effects [162], leading
above.Beyondtheseingredients,certainfruitscontainpartic- to speculation that these effects may simply be derived
ularcompoundssuchasanthocyaninsandbromelain,which fromgrape-derivedantioxidantsinthewine.However,other
may also be anti-inflammatory[147–151]. Anthocyaninsare alcoholic beverages such as beer and liquor have also been
the pigments found in fruits such as strawberries, cherries, found to have anti-inflammatory properties [163]. Overall,
blackberries, and black currants. Research has indicated thisimplicatessmalldosesofalcoholtobeanti-inflammatory.
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