PrescribingOptimalNutritionandPhysicalActivityas “First-Line ... · 2017-01-11 · field report...

28
Hindawi Publishing Corporation Arthritis Volume 2012, Article ID 560634, 28 pages doi:10.1155/2012/560634 Review Article Prescribing Optimal Nutrition and Physical Activity as “First-Line” Interventions for Best Practice Management of Chronic Low-Grade Inflammation Associated with Osteoarthritis: Evidence Synthesis Elizabeth Dean 1 and Rasmus Gormsen Hansen 2 1 Department of Physical Therapy, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada V6T 1Z3 2 Department of Physical Therapy, Ringsted and Slagelse Hospitals, Region Zealand, Denmark Correspondence should be addressed to Elizabeth Dean, [email protected] Received 7 August 2012; Revised 23 November 2012; Accepted 24 November 2012 Academic Editor: Pierre Youinou Copyright © 2012 E. Dean and R. Gormsen Hansen. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Low-grade inflammation and oxidative stress underlie chronic osteoarthritis. Although best-practice guidelines for osteoarthritis emphasize self-management including weight control and exercise, the role of lifestyle behavior change to address chronic low- grade inflammation has not been a focus of first-line management. This paper synthesizes the literature that supports the idea in which the Western diet and inactivity are proinflammatory, whereas a plant-based diet and activity are anti-inflammatory, and that low-grade inflammation and oxidative stress underlying osteoarthritis often coexist with lifestyle-related risk factors and conditions. We provide evidence-informed recommendations on how lifestyle behavior change can be integrated into “first- line” osteoarthritis management through teamwork and targeted evidence-based interventions. Healthy living can be exploited to reduce inflammation, oxidative stress, and related pain and disability and improve patients’ overall health. This approach aligns with evidence-based best practice and holds the promise of eliminating or reducing chronic low-grade inflammation, attenuating disease progression, reducing weight, maximizing health by minimizing a patient’s risk or manifestations of other lifestyle-related conditions hallmarked by chronic low-grade inflammation, and reducing the need for medications and surgery. This approach provides an informed cost effective basis for prevention, potential reversal, and management of signs and symptoms of chronic osteoarthritis and has implications for research paradigms in osteoarthritis. 1. Introduction Best practice guidelines for chronic osteoarthritis focus on self-management, that is, weight control and physical activity, and on pharmacological support for inflammation and pain [1–5]. Despite such guidelines, authorities in the field report a lack of efficacy of current treatments and associated adverse effects [6], with some proposing even greater attention to self-management [7]. Further, although low-grade inflammation underlies chronic osteoarthritis comparable to other conditions with significant lifestyle- related components often presenting concurrently with osteoarthritis, this inflammation has not been a focus of best practice guidelines, particularly of its nonpharmacologic management. To establish the prescription of optimal nutrition and physical activity as “first-line” interventions for low-grade inflammation associated with chronic osteoarthritis, we have synthesized three primary lines of support: (1) the literature that supports that the western diet and inactive lifestyle are proinflammatory, and a plant-based diet and regular physical activity are anti-inflammatory; (2) the literature supporting that low-grade inflammation is common across lifestyle- related conditions including osteoarthritis; and (3) evidence- informed recommendations for effecting lifestyle behavior change that can be readily integrated by health practitioners

Transcript of PrescribingOptimalNutritionandPhysicalActivityas “First-Line ... · 2017-01-11 · field report...

Page 1: PrescribingOptimalNutritionandPhysicalActivityas “First-Line ... · 2017-01-11 · field report a lack of efficacy of current treatments and associated adverse effects [6], ...

Hindawi Publishing CorporationArthritisVolume 2012, Article ID 560634, 28 pagesdoi:10.1155/2012/560634

Review Article

Prescribing Optimal Nutrition and Physical Activity as“First-Line” Interventions for Best Practice Management ofChronic Low-Grade Inflammation Associated with Osteoarthritis:Evidence Synthesis

Elizabeth Dean1 and Rasmus Gormsen Hansen2

1 Department of Physical Therapy, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada V6T 1Z32 Department of Physical Therapy, Ringsted and Slagelse Hospitals, Region Zealand, Denmark

Correspondence should be addressed to Elizabeth Dean, [email protected]

Received 7 August 2012; Revised 23 November 2012; Accepted 24 November 2012

Academic Editor: Pierre Youinou

Copyright © 2012 E. Dean and R. Gormsen Hansen. This is an open access article distributed under the Creative CommonsAttribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work isproperly cited.

Low-grade inflammation and oxidative stress underlie chronic osteoarthritis. Although best-practice guidelines for osteoarthritisemphasize self-management including weight control and exercise, the role of lifestyle behavior change to address chronic low-grade inflammation has not been a focus of first-line management. This paper synthesizes the literature that supports the ideain which the Western diet and inactivity are proinflammatory, whereas a plant-based diet and activity are anti-inflammatory,and that low-grade inflammation and oxidative stress underlying osteoarthritis often coexist with lifestyle-related risk factorsand conditions. We provide evidence-informed recommendations on how lifestyle behavior change can be integrated into “first-line” osteoarthritis management through teamwork and targeted evidence-based interventions. Healthy living can be exploited toreduce inflammation, oxidative stress, and related pain and disability and improve patients’ overall health. This approach alignswith evidence-based best practice and holds the promise of eliminating or reducing chronic low-grade inflammation, attenuatingdisease progression, reducing weight, maximizing health by minimizing a patient’s risk or manifestations of other lifestyle-relatedconditions hallmarked by chronic low-grade inflammation, and reducing the need for medications and surgery. This approachprovides an informed cost effective basis for prevention, potential reversal, and management of signs and symptoms of chronicosteoarthritis and has implications for research paradigms in osteoarthritis.

1. Introduction

Best practice guidelines for chronic osteoarthritis focuson self-management, that is, weight control and physicalactivity, and on pharmacological support for inflammationand pain [1–5]. Despite such guidelines, authorities in thefield report a lack of efficacy of current treatments andassociated adverse effects [6], with some proposing evengreater attention to self-management [7]. Further, althoughlow-grade inflammation underlies chronic osteoarthritiscomparable to other conditions with significant lifestyle-related components often presenting concurrently withosteoarthritis, this inflammation has not been a focus of

best practice guidelines, particularly of its nonpharmacologicmanagement.

To establish the prescription of optimal nutrition andphysical activity as “first-line” interventions for low-gradeinflammation associated with chronic osteoarthritis, we havesynthesized three primary lines of support: (1) the literaturethat supports that the western diet and inactive lifestyle areproinflammatory, and a plant-based diet and regular physicalactivity are anti-inflammatory; (2) the literature supportingthat low-grade inflammation is common across lifestyle-related conditions including osteoarthritis; and (3) evidence-informed recommendations for effecting lifestyle behaviorchange that can be readily integrated by health practitioners

Page 2: PrescribingOptimalNutritionandPhysicalActivityas “First-Line ... · 2017-01-11 · field report a lack of efficacy of current treatments and associated adverse effects [6], ...

2 Arthritis

into “first-line” management. We conclude with implicationsfor clinical practice and research with respect to its paradigmand avenues for future investigation.

2. Low-Grade Inflammation and Lifestyle

Human lifestyles have changed dramatically over millennia.With technological and economic advancements in westerncountries particularly over the past 60 years, lifestyle-relatedconditions are the leading causes of premature death [13].With globalization, western diets coupled with inactivityhave contributed largely to lifestyle-related conditions whichare increasingly prevalent in middle- and low-income coun-tries [14]. Some authorities have not only argued that west-ern diets have contributed to poor chronic health outcomes,but that national food guidelines such as those in the UnitedStates have legitimized poor nutrition for several decadesfurther contributing to the pandemic of lifestyle-relatedconditions [15]. In particular, poor nutritional quality hasbeen reported to contribute to obesity [16], a primary riskfactor for osteoarthritis [17], in addition to calorie density.

The factors associated with the typical western lifestylethat impact people’s health have been elucidated by cross-cultural studies including seminal work related to Mediter-ranean diet and exercise patterns and Asian lifestyles. TheMediterranean diet known to be health protective is largelyplant based, favors olive oil over animal fats, and is highin fiber, vegetables, and fruits [18]. The China study [19–22] is a prime example. This comprehensive series ofstudies has shown the serious health consequences of highconsumption of meat, dairy, fat, and refined grains andsugar (proinflammatory), and low consumption of wholegrains, vegetables and fruits, and legumes and pulses (anti-inflammatory). This unnatural diet for humans contributesto low-grade systemic inflammation and oxidative tissuestress and irritation, placing the immune system in anoveractive state, a common denominator of conditions withlifestyle components including arthritis [15]. Both high car-bohydrate and high fat consumption contribute to inflam-matory and oxidative stress even in healthy people [23].This effect could accentuate inflammatory conditions suchas lowering the threshold for local inflammation in arthritis.Diet-induced weight loss in people who are overweightreduces chronic low-grade inflammation as evidenced bysignification reduced C-reactive protein, an inflammationbiomarker [24].

In addition, sedentary living and inactivity are hallmarksof western culture. Evidence supports that inactivity is proin-flammatory and augments oxidative stress [25], whereasactivity when not excessive is anti-inflammatory [26, 27].More commonly understood about exercise, however, is thatinactivity weakens muscles and contributes to joint stress,in addition to reducing stimulation of synovial fluid whichcushions the joints and protects the joint spaces [28]. Activityand exercise continue to be primarily recommended andprescribed to people with arthritis to offset these adverseeffects. The anti-inflammatory effects of exercise, however,have been well established, and that for maximal anti-inflammatory benefit, broad-based training needs to include

resistance and aerobic training [26, 27, 29]. Exercise inducedanalgesia [30] and stiffness associated with osteoarthritismay reflect both its anti-inflammatory and mechanicaleffects; however, exercise’s anti-inflammatory effects are notdiscussed in established practice guidelines [1–5]. In sum, thewestern lifestyle is inherently unhealthy, and lifestyles withnonwestern diets and greater activity levels are typically asso-ciated with better health outcomes, for example, traditionalAsian and Mediterranean lifestyles [18, 31].

Other lifestyle traits common in western culture arealso known to be proinflammatory. Smoking, for example,remains prevalent despite some success in recent decadesin reducing its prevalence through public health campaigns.The chronic low-grade inflammation associated with smok-ing [32, 33] has been linked with inflammatory states associ-ated with ischemic heart disease [34], rheumatoid arthritis[35], and osteoarthritis [36]. Low-grade inflammation hasbeen associated with chronic sleep deprivation and stress[37–40] which are also common in western cultures. Giventhe well-documented link between low-grade inflammationand oxidative stress, and sleep deprivation and stress [41], acase can be made for assessing and addressing these in theinitial assessment and in first-line management of chronicosteoarthritis. In addition, sleep deprivation and stress arecommon arthritic complaints secondary to discomfort andpain, lending further support for assessing sleep and stressin people with chronic osteoarthritis and intervening asindicated.

Thus, prescribing healthy living strategies in general aswell as optimal nutrition (of which weight loss is an addi-tional benefit) and regular physical activity are warranted asbeing first-line interventions in clinical practice guidelinesfor conditions such as osteoarthritis associated with chroniclow-grade inflammation. These conditions are described inthe next section and often coexist as comorbidities in peoplewith osteoarthritis.

3. Low-Grade Inflammation andLifestyle-Related ConditionsIncluding Osteoarthritis

Figure 1 illustrates the interactive relationship amongosteoarthritis, obesity, and physical inactivity. Obesity is anindependent risk factor for osteoarthritis [84]. Althoughthe mechanisms for this association are not completelyunderstood, biomechanical loading and metabolic inflam-mation associated with excess adipose tissue and lipidsmay have a role. Pain associated with osteoarthritis leadsto increasingly less activity and psychosocial and physicaldisability. Physical inactivity is an independent risk factorfor inflammation due to the reduced expression of sys-temic and cellular anti-inflammatory mediators. Physiologiccyclic loading of cartilage tissue reduces the expression ofproinflammatory mediators and decreases cytokine-inducedextracellular matrix degradation. Physical inactivity reducesdaily energy expenditure thereby promoting weight gain andcontinuation of the cycle. Emerging evidence indicates thatosteoarthritis likely impedes the management of chronic

Page 3: PrescribingOptimalNutritionandPhysicalActivityas “First-Line ... · 2017-01-11 · field report a lack of efficacy of current treatments and associated adverse effects [6], ...

Arthritis 3

Physical inactivity

Altered biomechanicsJoint stiffnessJoint pain

Physical limitations

Energetic imbalance

Proinflammatory

effects of diet

Adipose tissue

inflammatory effectsChronic low-grade

systemic

inflammation

OverweightObesity OsteoarthritisPsychosocial disability

Figure 1: Relationships among osteoarthritis, obesity, and physical inactivity and relationship to the etiology of chronic low-grade systemicinflammation. Adapted from [8].

metabolic conditions associated with prolonged negativelifestyle habits such as obesity, type 2 diabetes mellitus, andischemic heart disease, because of its negative impact onphysical activity.

Table 1 shows evidence for chronic low-grade inflam-mation and oxidative stress in people with osteoarthritis.Multiple comorbidities that share comparable underlyingchronic low-grade inflammation and oxidative stress oftencoexist in individuals with chronic osteoarthritis, Examplesof these conditions and synthesis of the evidence appearin Table 2, for example, atherosclerosis, chronic cancer,chronic obstructive lung disease, diabetes, hypertension,insulin resistance and metabolic syndrome, ischemic heartdisease, obesity, and stroke. Almost 20 percent of Americanadults report having physician-diagnosed arthritis, and thisis expected to increase over the next two decades [88].Based on the Behavioral Risk Factor Surveillance Systemand National Health Interview Survey in the United States,individuals with osteoarthritis have a high incidence of otherlifestyle-related conditions with inflammatory componentsthat often present comorbidly with osteoarthritis (see exam-ples in Table 2). Our search strategy used keywords includinglifestyle-related conditions, chronic low-grade or chronicsystemic inflammation. This synthesis of evidence reflectsthe literature indexed in established electronic data bases(MEDLINE and PubMed) and primarily published over thepast five years. However, in several instances, importantrelated work that was published earlier has been includedin this evidence synthesis. The literature extracted representsa breadth of scholarly paradigms including clinical trials,cross-sectional population-based studies, experimental trialsbased on basic science and models and histological evidence,expert narrative reviews, randomized controlled clinicaltrials, and systematic reviews.

Although the degree to which the typical western lifestyleexplains the prevalence of osteoarthritis is unclear, maxi-mizing healthy living may have the greatest potential forminimizing its risk, its impact, and long-term outcomes

including life-long health and wellbeing compared withinvasive interventions including drugs and surgery and theirrelated sequelae and side effects.

Overweight is now considered a leading condition asso-ciated with marked inflammation followed by arthritis, heartdisease, and type 2 diabetes mellitus [89]. The mechanismwhereby overweight contributes to inflammation is reportedto involve high fat content of the diet [90]. Thus, promotinghealthy weight through healthy nutrition in addition toregular physical activity and exercise is critically important topromote a maximally anti-inflammatory systemic environ-ment to offset low-grade inflammation as well as to achieveweight loss.

4. Integration of Lifestyle BehaviorChange into “First-Line” Management

For lifestyle behavior change to constitute “first-line” man-agement as the literature would support, the health careteam overall needs to share this goal and practice inpartnership rather than in the conventional siloed care.The three primary health professions excluding, dentistryand pharmacy, include physicians, nurses, and physicaltherapists. Traditionally, physicians are highly trained inadministration of invasive interventions, that is, drugs andsurgery. Nurses have assumed a role in patient education overthe years along with psychosocial considerations of patientcare. Of the established health professions, physical therapy isthe leading nonpharmacologic profession that is particularlywell positioned to assume such an education role for patientsrelated to healthy lifestyles and exercise [91, 92].

Consistent with the 21st century epidemiological trends,physical therapists are moving toward a model of carebased on health (International Classification of Functioning,Disability and Health) [91, 93], which includes initiatingand supporting behavior change such as optimal nutrition,weight reduction, reduced sedentary activity, and increased

Page 4: PrescribingOptimalNutritionandPhysicalActivityas “First-Line ... · 2017-01-11 · field report a lack of efficacy of current treatments and associated adverse effects [6], ...

4 Arthritis

Ta

ble

1:Sy

nth

esis

ofev

iden

ceof

chro

nic

low

-gra

dein

flam

mat

ion

bein

gas

soci

ated

wit

hos

teoa

rth

riti

s.

Au

thor

sT

itle

Evid

ence

clas

sifi

cati

onM

eth

ods

Fin

din

gsC

oncl

usi

on

Cec

ilet

al.,

2005

Th

eJo

urn

alof

Imm

un

olog

y[9

]

Infl

amm

atio

n-

indu

ced

chon

droc

yte

hyp

ertr

ophy

isdr

iven

byre

cept

orfo

rad

van

ced

glyc

atio

nen

dpr

odu

cts

Bas

icsc

ien

cest

udy

Exp

erim

enta

lstu

dy

An

alys

isof

hum

anca

rtila

ge,c

ult

ure

dhu

man

arti

cula

rch

ondr

ocyt

es,a

nd

reco

mbi

nan

thu

man

S100

A11

,so

lubl

eR

AG

E(a

dvan

ced

glyc

atio

nen

dpr

odu

cts)

,an

dR

AG

E-s

peci

fic

bloc

kin

gan

tibo

dies

Nor

mal

hum

ankn

eeca

rtila

ges

show

edco

nst

itu

tive

RA

GE

and

S100

A11

expr

essi

on,a

nd

RA

GE

and

S100

A11

expr

essi

onw

ere

upr

egu

late

din

OA

cart

ilage

s

Up-

regu

late

dch

ondr

ocyt

eex

pres

sion

inO

Aca

rtila

gean

dR

AG

Esi

gnal

ing

prom

ote

infl

amm

atio

n-

asso

ciat

edch

ondr

ocyt

ehy

per

trop

hy

Roj

as-R

odrı

guez

etal

.,20

07M

edic

alH

ypot

hes

es[1

0]

Th

ere

lati

onbe

twee

nth

em

etab

olic

syn

drom

ean

den

ergy

-uti

lizat

ion

defi

cit

inth

epa

thog

enes

isof

obes

ity-

indu

ced

oste

oart

hri

tis

Nar

rati

vere

view

toex

amin

ea

med

ical

hypo

thes

is:

path

ogen

esis

ofob

esit

y-in

duce

dO

Am

aybe

expl

ain

edby

met

abol

icch

ange

sin

stri

ated

mu

scle

byin

tera

ctio

nof

insu

linre

sist

ance

and

syst

emic

infl

amm

atio

nin

obes

ein

divi

dual

s

Evid

ence

sear

chst

rate

gyu

nsp

ecifi

ed

Incr

ease

dT

H1

cyto

kin

esar

epr

odu

ced

bym

acro

phag

esin

pres

ence

ofch

ron

icin

fect

ion

and

supp

ress

insu

linse

nsi

tivi

tyM

usc

lece

llsan

dad

ipoc

ytes

are

acti

vate

dby

infl

amm

ator

ycy

toki

nes

and

con

trib

ute

toch

ron

iclo

w-g

rade

infl

amm

atio

nin

appa

ren

tly

hea

lthy

obes

ein

divi

dual

s

Th

efa

tigu

ean

dm

usc

lew

eakn

ess

indu

ced

byin

sulin

resi

stan

cean

din

flam

mat

ion

inob

ese

pati

ents

wit

hm

etab

olic

syn

drom

e(p

ro-i

nfl

amm

ator

yst

ate)

incr

ease

trau

ma

tojo

ints

that

resu

ltin

brea

kin

gof

ten

oper

iost

eal

jun

ctio

nan

dab

rasi

veda

mag

eof

cart

ilage

Page 5: PrescribingOptimalNutritionandPhysicalActivityas “First-Line ... · 2017-01-11 · field report a lack of efficacy of current treatments and associated adverse effects [6], ...

Arthritis 5

Ta

ble

1:C

onti

nu

ed.

Au

thor

sT

itle

Evid

ence

clas

sifi

cati

onM

eth

ods

Fin

din

gsC

oncl

usi

on

Sch

lesi

nge

ran

dT

hie

le,2

010

An

nal

sof

Rh

eum

atic

Dis

ease

s[1

1]

Th

epa

thog

enes

isof

bon

eer

osio

ns

are

ingo

uty

arth

riti

s

Rev

iew

Syn

thes

isof

mec

han

ical

,pa

thol

ogic

al,

cellu

lar,

and

imm

un

olog

ical

fact

ors

role

inth

epa

thog

enes

isof

bon

eer

osio

ns

ingo

uty

arth

riti

sSe

arch

stra

tegy

un

spec

ified

Mon

osod

ium

ura

tecr

ysta

ldep

osit

ion

asso

ciat

edw

ith

un

derl

yin

gO

AG

outy

toph

us

and

bon

eer

osio

ns

asso

ciat

edw

ith

chro

nic

low

-gra

dein

flam

mat

ion

Toph

us

erod

ing

un

derl

yin

gbo

ne

ispi

vota

lfor

deve

lopm

ent

ofbo

ne

eros

ion

sin

gou

tyar

thri

tis

Smit

het

al.1

997

Jou

rnal

ofR

heu

mat

olog

y[1

2]

Syn

ovia

lm

embr

ane

infl

amm

atio

nan

dcy

toki

ne

prod

uct

ion

inpa

tien

tsw

ith

earl

yos

teoa

rth

riti

s

Clin

ical

tria

lof

pati

ents

wit

hva

ryin

gst

ages

ofea

rly

OA

(n=

63)

Syn

ovia

lm

embr

ane

sam

ples

obta

ined

from

the

knee

sof

pati

ents

Th

icke

nin

gof

linin

gla

yer,

incr

ease

dva

scu

lari

ty,a

nd

infl

amm

ator

yce

llin

filt

rati

onin

syn

ovia

lm

embr

anes

;ch

ange

spr

opor

tion

alto

seve

rity

Infl

amm

ator

ym

arke

rsin

crea

sed

inth

esy

nov

ial

mem

bran

esof

pati

ents

irre

spec

tive

ofde

gree

ofar

ticu

lar

dam

age

Ch

ron

icin

flam

mat

ory

chan

ges

wit

hpr

odu

ctio

nof

pro-

infl

amm

ator

ycy

toki

nes

char

acte

rize

the

syn

ovia

lm

embr

anes

ofpa

tien

tsw

ith

earl

yO

ALo

w-g

rade

syn

ovit

isre

sult

sin

the

prod

uct

ion

ofcy

toki

nes

that

may

con

trib

ute

toO

Apa

thog

enes

is

Page 6: PrescribingOptimalNutritionandPhysicalActivityas “First-Line ... · 2017-01-11 · field report a lack of efficacy of current treatments and associated adverse effects [6], ...

6 Arthritis

Ta

ble

2:Sy

nth

esis

ofev

iden

ceof

chro

nic

low

-gra

dein

flam

mat

ion

bein

gas

soci

ated

wit

hco

ndi

tion

sth

atm

ayco

exis

tw

ith

adi

agn

osis

ofos

teoa

rth

riti

s.

Alz

hei

mer

’sdi

seas

e

Giu

nta

etal

.,20

08Jo

urn

alof

Neu

roin

flam

mat

ion

[42]

Infl

amm

agin

gas

apr

odro

me

toA

lzh

eim

er’s

dise

ase

Rev

iew

Th

eim

mu

nol

ogic

alas

pect

sof

agin

gre

late

dto

Alz

hei

mer

’sD

isea

se(A

D),

that

is,t

he

incr

ease

din

nat

eim

mu

nit

yby

cells

ofth

em

onon

ucl

ear

Art

icle

sre

port

edth

ech

arac

teri

zati

onth

eag

ing

imm

un

ere

spon

sere

late

dto

the

con

cept

ofin

flam

mag

ing

(low

-gra

dech

ron

icu

p-re

gula

tion

ofpr

o-in

flam

mat

ory

resp

onse

)Sp

ecifi

cse

arch

stra

tegy

un

spec

ified

Con

diti

ons

ofin

crea

sed

inn

ate

imm

un

ere

spon

sew

ith

over

prod

uct

ion

ofpr

o-in

flam

mat

ory

prot

ein

sar

ere

late

dto

hea

lthy

agin

gan

dA

DPe

ople

wh

oag

e“w

ell”

hav

ean

ti-i

nfl

amm

agin

gm

ech

anis

ms

and

biom

arke

rsth

atco

un

ter

the

adve

rse

imm

un

ere

spon

seof

infl

amm

agin

g

Cou

nte

rin

gin

flam

mag

ing

may

prev

ent

ortr

eat

the

sym

ptom

sof

AD

Vee

rhu

is,2

011

Cu

rren

tA

lzh

eim

erR

esea

rch

[43]

His

tolo

gica

lan

ddi

rect

evid

ence

for

the

role

ofco

mpl

emen

tin

the

neu

roin

flam

mat

ion

ofA

D(A

D-A

lzh

eim

er’s

dise

ase)

His

tolo

gic

and

dire

ctev

iden

ce

Syn

thes

isan

dse

cret

ion

ofre

acti

veox

ygen

spec

ies

(RO

S),c

ytok

ines

,ch

emok

ines

,an

dot

her

pote

nti

ally

neu

roto

xic

agen

tsby

the

glia

lcel

lsim

plic

ated

inA

D

InA

D,t

her

ear

ebr

ain

area

sw

ith

amyl

oid

depo

sits

and

com

plem

ent

acti

vati

onpr

odu

cts

Com

plem

ent

regu

lato

rypr

otei

ns

are

fou

nd

inbr

ain

pare

nch

yma

and

are

upr

egu

late

d,es

pec

ially

un

der

infl

amm

ator

yco

ndi

tion

s

Evid

ence

from

imm

un

ohis

toch

emic

al,

invi

tro

and

anim

alst

udi

esp

oin

tsto

role

for

com

plem

ent

acti

vati

onIn

chro

nic

low

-gra

dein

flam

mat

ory

con

diti

ons,

such

asin

AD

,com

plem

ent

acti

vati

onpr

ocee

ds,

lead

ing

tosu

stai

ned

glia

lce

llac

tiva

tion

and

neu

rode

gen

erat

ive

chan

ges

Can

dore

etal

.,20

10C

urr

ent

Ph

arm

acol

ogy

Des

ign

s[4

4]

Low

grad

ein

flam

mat

ion

asa

com

mon

path

ogen

etic

den

omin

ator

inag

e-re

late

ddi

seas

es:

nov

eldr

ug

targ

ets

for

anti

-age

ing

stra

tegi

esan

dsu

cces

sfu

lage

ing

ach

ieve

men

t

Rev

iew

Sear

chst

rate

gyu

nsp

ecifi

ed

Evid

ence

supp

orts

that

low

-gra

desy

stem

icin

flam

mat

ion

char

acte

rize

sag

ein

gan

dth

atin

flam

mat

ory

mar

kers

are

sign

ifica

nt

pred

icto

rsof

mor

talit

yw

ith

agei

ng

Elu

cida

tion

ofag

ein

gpa

thop

hysi

olog

yto

dise

nta

ngl

eag

e-re

late

dlo

w-g

rade

infl

amm

atio

nw

illpr

ovid

eev

iden

ceto

deve

lop

dru

gsto

dela

yag

ein

gpr

oces

s

Page 7: PrescribingOptimalNutritionandPhysicalActivityas “First-Line ... · 2017-01-11 · field report a lack of efficacy of current treatments and associated adverse effects [6], ...

Arthritis 7

Ta

ble

2:C

onti

nu

ed.

Ast

hm

a

Ch

ouet

al.,

2011

Jou

rnal

ofSe

xM

edic

ine

[45]

Ast

hm

aan

dri

skof

erec

tile

dysf

un

ctio

n—

an

atio

nwid

epo

pula

tion

-bas

edsu

rvey

Popu

lati

on-b

ased

surv

eybe

twee

n20

00an

d20

07,

new

lydi

agn

osed

asth

ma

case

sid

enti

fied

(18–

55y)

(n=

3466

)C

ontr

olco

hor

t(w

ith

out

asth

ma)

mat

ched

for

age

and

co-m

orbi

diti

es(n=

13,8

36)

Coh

orts

wer

efo

llow

edfo

rev

iden

ceof

erec

tile

dysf

un

ctio

n(E

D)

Subj

ects

wit

has

thm

aex

per

ien

ced

1.9-

fold

incr

ease

inE

Din

depe

nde

nt

ofag

ean

dco

mor

bidi

tyco

mpa

red

wit

hco

ntr

olco

hor

t

Ast

hm

am

aybe

anin

depe

nde

nt

risk

fact

orfo

rE

D(i

ncr

easi

ng

wit

has

thm

ase

veri

ty)

Ch

ron

icsy

stem

icin

flam

mat

ion

isim

plic

ated

inth

islin

kage

Dix

on,2

012

Exp

ert

Rev

iew

sin

Res

pira

tory

Med

icin

e[4

6]

Th

etr

eatm

ent

ofas

thm

ain

obes

ity

Exp

ert

revi

ew

Epi

dem

iolo

gyof

obes

ity

has

infl

uen

ced

epid

emio

logy

ofot

her

con

diti

ons,

for

exam

ple,

asth

ma

Obe

sity

maj

orri

skfa

ctor

for

new

asth

ma

Sear

chst

rate

gyn

otsp

ecifi

ed

Mec

han

ical

fact

ors,

met

abol

icin

flam

mat

ion

,an

dot

her

com

orbi

diti

espr

obab

lyco

ntr

ibu

teto

asth

ma

Th

erap

ies

nee

dto

bede

velo

ped

and

tailo

red

tova

riou

su

nde

rlyi

ng

mec

han

ism

s

Juel

etal

.,20

12Jo

urn

alof

Ast

hm

aan

dA

llerg

y[4

7]

Ast

hm

aan

dob

esit

y:do

esw

eigh

tlo

ssim

prov

eas

thm

aco

ntr

ol?

Asy

stem

atic

revi

ew

Syst

emat

icre

view

Obe

sity

asso

ciat

edw

ith

hig

has

thm

ain

cide

nce

and

poor

con

trol

Rev

iew

ofkn

owle

dge

oneff

ect

ofw

eigh

tre

duct

ion

onas

thm

aco

ntr

olba

sed

onsy

stem

atic

sear

ches

usi

ng

the

Pu

bMed

data

base

and

rele

van

tM

eSH

term

s

Wei

ght

loss

inob

ese

indi

vidu

als

asso

ciat

edw

ith

48%

–100

%re

mis

sion

ofas

thm

asy

mpt

oms

Wei

ght

loss

asso

ciat

edw

ith

impr

oved

lun

gfu

nct

ion

and

airw

ayre

spon

sive

nes

sto

inh

aled

met

hac

hol

ine

Wei

ght

loss

con

sist

entl

yre

duce

sas

thm

asy

mpt

oms

Impr

oved

asth

ma

con

trol

incl

udi

ng

obje

ctiv

em

easu

res

ofdi

seas

eac

tivi

ty

Ath

eros

cler

osis

Gu

etal

.,20

12A

ther

oscl

eros

is[4

8]

Psyc

hol

ogic

alst

ress

,im

mu

ne

resp

onse

,an

dat

her

oscl

eros

isR

evie

w

Syn

thes

isof

evid

ence

sth

atva

riou

sim

mu

nol

ogic

alfa

ctor

sar

etr

ansf

orm

edu

nde

rpr

olon

ged

psyc

hol

ogic

alst

ress

byca

usi

ng

vasc

ula

rlo

w-g

rade

infl

amm

atio

n

Evid

ence

supp

orts

expr

essi

onof

pro-

and

anti

-in

flam

mat

ory

cyto

kin

esby

stre

ssh

orm

ones

(cat

ech

olam

ines

and

cort

icos

tero

ids)

Elu

cida

tion

oftw

o-w

ayco

mm

un

icat

ion

betw

een

neu

roen

docr

ine

and

imm

un

esy

stem

sIm

plic

atio

ns

for

targ

eted

trea

tmen

tst

rate

gies

Page 8: PrescribingOptimalNutritionandPhysicalActivityas “First-Line ... · 2017-01-11 · field report a lack of efficacy of current treatments and associated adverse effects [6], ...

8 Arthritis

Ta

ble

2:C

onti

nu

ed.

Ku

char

z,20

12M

edic

alH

ypot

hes

es[4

9]

Ch

ron

icin

flam

mat

ion

-en

han

ced

ath

eros

cler

osis

:can

we

con

side

rit

an

ewcl

inic

alsy

ndr

ome?

Nar

rati

vere

view

Med

ical

hypo

thes

is:

inci

den

ceof

card

iova

scu

lar

dise

ase

(CV

D)

inpa

tien

tsw

ith

chro

nic

auto

imm

un

edi

sord

ers

ism

uch

hig

her

than

inge

ner

alpo

pula

tion

CV

Dis

cau

sed

byac

cele

rate

dat

her

oscl

eros

is,i

nw

hic

hch

ron

icin

flam

mat

ion

isim

plic

ated

Th

elit

erat

ure

sear

chst

rate

gies

un

spec

ified

Ch

ron

icin

flam

mat

ion

-en

han

ced

ath

eros

cler

osis

syn

drom

eis

prop

osed

asa

sepa

rate

syn

drom

eoc

curr

ing

inpa

tien

tssu

ffer

ing

ofch

ron

icin

flam

mat

ion

Ath

eros

cler

osis

asan

infl

amm

ator

ydi

seas

ean

dch

ron

icex

trav

ascu

lar

infl

amm

atio

nh

ave

com

mon

mec

han

ism

sre

sult

ing

inan

incr

ease

inat

her

oscl

eros

isan

dit

sse

quel

ae,C

VD

Luet

al.,

2012

Psyc

hos

omat

icM

edic

ine

[50]

Un

pred

icta

ble

chro

nic

mild

stre

sspr

omot

esat

her

oscl

eros

isin

hig

hch

oles

tero

l-fe

dra

bbit

s

Exp

erim

enta

l

Ch

ron

icps

ych

olog

ical

stre

ssas

soci

ated

incr

ease

dw

ith

risk

ofat

her

oscl

eros

isSt

udy

ofeff

ects

ofch

ron

icst

ress

onat

her

ogen

esis

inra

bbit

sR

abbi

tsfe

dch

oles

tero

l-ri

chdi

etfo

r4–

16w

ks

Hig

h-c

hol

este

rolf

eedi

ng

resu

lted

inhy

per

chol

este

role

mia

and

form

atio

nof

ath

eros

cler

otic

plaq

ues

inth

eao

rta

Hig

h-c

hol

este

rold

iet

incr

ease

dpl

aqu

esi

zean

din

stab

ility

Fin

din

gssu

ppor

tth

atat

her

oscl

eros

isis

augm

ente

dby

chro

nic

psyc

hol

ogic

alst

ress

,du

eto

incr

ease

dva

scu

lar

infl

amm

atio

nan

dde

crea

sed

endo

thel

ial

nit

ric

oxid

ebi

oava

ilabi

lity

Ort

ega

etal

.,20

12A

ther

oscl

eros

is[5

1]

Wh

ite

bloo

dce

llco

un

tis

asso

ciat

edw

ith

caro

tid

and

fem

oral

ath

eros

cler

osis

Clin

ical

stu

dySu

bjec

tsw

ith

dysl

ipid

emia

(n=

554)

and

sex-

mat

ched

nor

mol

ipid

emic

subj

ects

(n=

246)

Exa

min

edth

eas

soci

atio

nbe

twee

nin

flam

mat

ory

mar

kers

and

ath

eros

cler

osis

evid

ence

Car

otid

and

fem

oral

arte

ries

wer

eim

aged

Wh

ite

bloo

dce

llco

un

ts(W

BC

C)

wer

eob

tain

ed

Ch

ron

iclo

w-g

rade

infl

amm

atio

nis

asso

ciat

edw

ith

ath

eros

cler

osis

WB

CC

asso

ciat

edw

ith

mea

sure

sof

ath

eros

cler

osis

inde

pen

den

tof

risk

fact

ors

WB

CC

isa

use

fula

nd

easy

mar

ker

ofat

her

oscl

eros

is,

con

sist

ent

wit

hit

sin

flam

mat

ory

basi

s

Pin

toet

al.,

2012

Cu

rren

tP

har

mac

euti

cal

Des

ign

[52]

Eff

ects

ofph

ysic

alex

erci

seon

infl

amm

ator

ym

arke

rsof

ath

eros

cler

osis

Exp

ert

nar

rati

vere

view

Syn

thes

isof

rese

arch

rela

ted

tore

gula

rph

ysic

altr

ain

ing

and

low

-gra

dein

flam

mat

ion

Sear

chst

rate

gyu

nsp

ecifi

ed

Phy

sica

lexe

rcis

eco

uld

beco

nsi

dere

da

use

ful

wea

pon

agai

nst

loca

lva

scu

lar

and

syst

emic

infl

amm

atio

nin

ath

eros

cler

osis

.

Seve

ralm

ech

anis

ms

expl

ain

the

posi

tive

effec

tof

chro

nic

exer

cise

Incl

udi

ng

decr

ease

din

flam

mat

ion

and

endo

thel

iald

ysfu

nct

ion

,an

dm

odu

late

dpr

ogre

ssio

nof

un

derl

yin

gdi

seas

epr

ogre

ss

Page 9: PrescribingOptimalNutritionandPhysicalActivityas “First-Line ... · 2017-01-11 · field report a lack of efficacy of current treatments and associated adverse effects [6], ...

Arthritis 9

Ta

ble

2:C

onti

nu

ed.

Can

cer

Cor

rea

and

Pia

zuel

o,20

12[5

3]T

he

gast

ric

prec

ance

rou

sca

scad

eLe

adar

ticl

eSt

ate-

of-t

he-

art

Rev

iew

ofex

per

imen

tal

arti

cles

that

supp

ort

the

step

sin

the

gast

ric

prec

ance

rou

sca

scad

eSe

arch

stra

tegy

un

spec

ified

Infl

amm

ator

ych

ange

sm

ayp

ersi

stth

rou

ghou

tth

epr

ecan

cero

us

proc

ess

Firs

tre

cogn

ized

his

tolo

gica

lch

ange

isac

tive

chro

nic

infl

amm

atio

nw

hic

his

the

firs

tst

epin

the

prec

ance

rou

sca

scad

e

Mos

tpr

omis

ing

stra

tegy

for

con

trol

ofth

eco

ndi

tion

ispr

even

tion

,au

gmen

ted

bypr

olon

gin

gth

epr

e-ca

nce

rou

spr

oces

sw

hic

hre

quir

esan

un

ders

tan

din

gof

the

prec

ance

rou

sca

scad

eLe

sion

dete

cted

earl

iest

inin

flam

mat

ion

Pete

rset

al.2

012

Stre

ss[5

4]

Ch

ron

icps

ych

osoc

ial

stre

ssin

crea

ses

the

risk

for

infl

amm

atio

n-r

elat

edco

lon

carc

inog

enes

isin

mal

em

ice

Exp

erim

enta

lA

nim

alm

odel

Inve

stig

ated

the

effec

tsof

chro

nic

psyc

hos

ocia

lst

ress

inm

ale

mic

ew

ith

arti

fici

ally

indu

ced

colo

rect

alca

nce

r(C

RC

)

Ou

tcom

esba

sed

onco

lon

osco

pic

eval

uat

ion

and

prot

ein

anal

ysis

CSC

mic

esh

owed

acce

lera

ted

mac

rosc

opic

lesi

ons

CSC

mic

esh

owed

mor

ece

lldy

spla

sia

than

the

sin

gle-

hou

sed

con

trol

(SH

C)

mic

eA

bnor

mal

prot

ein

expr

essi

onw

asal

sogr

eate

rin

CSC

than

SHC

mic

e

Fin

din

gsco

nsi

sten

tw

ith

the

fact

that

chro

nic

psyc

hos

ocia

lstr

ess

incr

ease

sth

elik

elih

ood

ofde

velo

pin

gan

irri

tabl

ebo

wel

,an

dm

ult

iple

typ

esof

mal

ign

ant

neo

plas

ms,

incl

udi

ng

CR

C

Ch

ron

icob

stru

ctiv

elu

ng

dise

ase

Cox

jr20

12D

ose

Res

pon

se[5

5]

Dos

e-re

spon

seth

resh

olds

for

prog

ress

ive

dise

ases

Nar

rati

vere

view

Topr

ovid

eev

iden

ceba

sefo

rfr

amew

ork

Fram

ewor

kpr

opos

edfo

ru

nde

rsta

ndi

ng

how

expo

sure

can

dest

abili

zen

orm

ally

hom

eost

atic

feed

back

con

trol

syst

ems

and

crea

tesu

stai

ned

imba

lan

ces

and

elev

ated

leve

lsof

dise

ase-

rela

ted

Th

ere

sult

ing

mod

el,

calle

dth

eal

tern

ativ

eeq

uili

bria

(AE

)th

eory

,im

plie

sth

eex

iste

nce

ofan

expo

sure

thre

shol

dbe

low

wh

ich

tran

siti

onto

the

alte

rnat

ive

equ

ilibr

ium

(pot

enti

aldi

seas

e)

Th

ese

pred

icti

ons

may

hel

pto

expl

ain

patt

ern

sob

serv

edin

exp

erim

enta

lan

dep

idem

iolo

gica

lda

tafo

rdi

seas

essu

chas

CO

PD

,sili

cosi

s,an

din

flam

mat

ion

-med

iate

dlu

ng

can

cer

Page 10: PrescribingOptimalNutritionandPhysicalActivityas “First-Line ... · 2017-01-11 · field report a lack of efficacy of current treatments and associated adverse effects [6], ...

10 Arthritis

Ta

ble

2:C

onti

nu

ed.

vari

able

s,by

crea

tin

ga

new

,loc

ally

stab

le,a

lter

nat

ive

equ

ilibr

ium

for

the

dyn

amic

syst

em,i

nad

diti

onto

its

nor

mal

(hom

eost

atic

)eq

uili

briu

mSe

arch

stra

tegy

un

spec

ified

stat

ew

illn

otoc

cur,

and

once

exce

eded

,pr

ogre

ssio

nto

the

alte

rnat

ive

equ

ilibr

ium

con

tin

ues

spon

tan

eou

sly,

even

wit

hou

tfu

rth

erex

posu

re

Lin

dber

get

al.,

2011

CO

PD

[56]

Co-

mor

bidi

tyin

mild

-to-

mod

erat

eC

OP

D:c

ompa

riso

nto

nor

mal

and

rest

rict

ive

lun

gfu

nct

ion

Clin

ical

tria

lSu

bjec

tsw

ith

CO

PD

from

obst

ruct

ive

lun

gdi

seas

ein

nor

ther

nSw

eden

coh

ort

follo

wed

in20

02–2

004

(n=

993)

Gen

der

and

age

mat

ched

refe

ren

cesu

bjec

tsw

ith

out

CO

PD

(n=

993)

Toev

alu

ate

ifco

ndi

tion

sas

soci

ated

wit

hsy

stem

icin

flam

mat

ion

(e.g

.,ca

rdio

vasc

ula

rdi

seas

es,

diab

etes

,ch

ron

icrh

init

is,

and

gast

roes

oph

agea

lre

flu

x,ar

eov

erre

pres

ente

din

pati

ents

wit

hC

OP

DA

nal

ysis

base

don

inte

rvie

wda

taon

co-m

orbi

dity

and

sym

ptom

s

Pre

vale

nce

ofch

ron

icrh

init

isan

dga

stro

esop

hag

ealr

eflu

x(G

ER

D)

was

hig

her

inC

OP

Dco

mpa

red

tore

fere

nce

grou

pIn

rest

rict

ive

lun

gfu

nct

ion

,th

epr

eval

ence

ofch

ron

icrh

init

is,

card

iova

scu

lar

dise

ase,

hype

rlip

emia

,an

ddi

abet

esw

ash

igh

erco

mpa

red

tore

fere

nce

grou

pIn

CO

PD

and

hea

rtdi

seas

e,ch

ron

icrh

init

isan

d/or

GE

RD

wer

epr

opor

tion

atel

yh

igh

erth

anre

fere

nce

grou

p

Co-

mor

bid

con

diti

ons

asso

ciat

edw

ith

syst

emic

infl

amm

atio

n,f

orex

ampl

e,ca

rdio

vasc

ula

rdi

seas

e,ch

ron

icrh

init

is,

and

gast

roes

oph

agea

lre

flu

x,w

ere

com

mon

inpa

tien

tsw

ith

CO

PD

Ove

rlap

betw

een

hea

rtdi

seas

e,ch

ron

icrh

init

isan

dG

ER

Dw

asla

rge

inC

OP

D

ten

Hac

ken

,200

9P

roce

edin

gof

the

Am

eric

anT

hor

acic

Soci

ety

[57]

Phy

sica

lin

acti

vity

and

obes

ity:

rela

tion

toas

thm

aan

dch

ron

icob

stru

ctiv

epu

lmon

ary

dise

ase?

Rev

iew

Tosu

mm

ariz

eth

eav

aila

ble

liter

atu

rere

gard

ing

the

pote

nti

alro

leof

phys

ical

inac

tivi

tyan

dob

esit

yin

asth

ma

and

CO

PD

and

toex

amin

eth

eir

con

trib

uti

onto

syst

emic

infl

amm

atio

n

Phy

sica

lin

acti

vity

and

obes

ity

are

asso

ciat

edw

ith

low

-gra

desy

stem

icin

flam

mat

ion

that

may

con

trib

ute

toth

ein

flam

mat

ory

proc

esse

spr

esen

tin

man

ych

ron

icdi

seas

esSe

arch

stra

tegy

un

spec

ified

Hig

hpr

eval

ence

ofas

thm

ain

obes

ity

Inch

ron

icob

stru

ctiv

epu

lmon

ary

dise

ase

(CO

PD

),ph

ysic

alin

acti

vity

has

been

dem

onst

rate

dT

his

was

asso

ciat

edw

ith

ah

igh

erde

gree

ofsy

stem

icin

flam

mat

ion

,

Elu

cida

tion

ofth

ein

depe

nde

nt

rela

tion

ship

betw

een

phys

ical

inac

tivi

tyan

dob

esit

yw

ith

syst

emic

infl

amm

atio

n,

perf

orm

ance

-bas

edst

udi

esof

phys

ical

inac

tivi

tyin

asth

ma

and

CO

PD

are

nee

ded

Page 11: PrescribingOptimalNutritionandPhysicalActivityas “First-Line ... · 2017-01-11 · field report a lack of efficacy of current treatments and associated adverse effects [6], ...

Arthritis 11

Ta

ble

2:C

onti

nu

ed.

inde

pen

den

tof

body

mas

sin

dex

Obe

sity

isas

soci

ated

wit

hth

ech

ron

icob

stru

ctiv

eph

enot

ype

and

feat

ure

sof

the

met

abol

icsy

ndr

ome

Wou

ters

etal

.,20

09P

roce

edin

gsof

the

Am

eric

anT

hor

acic

Soci

ety

[58]

Syst

emic

and

loca

lin

flam

mat

ion

inas

thm

aan

dch

ron

icob

stru

ctiv

epu

lmon

ary

dise

ase:

isth

ere

aco

nn

ecti

on?

Rev

iew

Stat

e-of

-th

e-ar

t

Toex

amin

eth

eas

soci

atio

nbe

twee

nas

thm

aan

dch

ron

icob

stru

ctiv

epu

lmon

ary

dise

ase

(CO

PD

)Se

arch

stra

tegy

un

spec

ified

Spill

over

ofin

flam

mat

ory

med

iato

rsin

toth

eci

rcu

lati

onco

nsi

dere

dth

eso

urc

eof

syst

emic

infl

amm

atio

nin

thes

eco

ndi

tion

s

Nat

ure

ofsy

stem

icin

flam

mat

ion

rem

ain

su

ncl

ear

Adi

pose

tiss

ue

med

iate

din

flam

mat

ion

ison

eex

plan

atio

n

Dia

bete

sm

ellit

us

(typ

es1

and

2)

Ch

ang

etal

.,20

12in

pres

sA

cta

Dia

beto

logi

ca[5

9]

Acu

tean

dch

ron

icfl

uct

uat

ion

sin

bloo

dgl

uco

sele

vels

can

incr

ease

oxid

ativ

est

ress

inty

pe2

diab

etes

mel

litu

s

Clin

ical

tria

lSu

bjec

ts:p

atie

nts

wit

hty

pe2

diab

etes

mel

litu

s(n=

34)

Toex

amin

ew

het

her

shor

t-or

lon

g-te

rmgl

ycem

icfl

uct

uat

ion

sco

uld

indu

ceox

idat

ive

stre

ssan

dch

ron

icin

flam

mat

ion

,re

lati

onsh

ips

betw

een

glyc

emic

vari

abili

ty,

oxid

ativ

est

ress

mar

kers

,an

dh

igh

-sen

siti

vity

C-r

eact

ive

prot

ein

(hs-

CR

P)

wer

est

udi

ed

Rel

atio

nsh

ips

betw

een

mar

kers

for

shor

t-an

dlo

ng-

term

glyc

emic

con

trol

rem

ain

edsi

gnifi

can

tw

ith

resp

ect

toox

idat

ive

stre

ssan

dch

ron

icin

flam

mat

ion

,af

ter

adju

stin

gfo

rot

her

mar

kers

ofdi

abet

icco

ntr

ol

Bot

hac

ute

and

chro

nic

bloo

dgl

uco

seva

riab

ility

can

indu

ceox

idat

ive

stre

ssan

dch

ron

icin

flam

mat

ion

van

Bu

ssel

etal

.,20

12in

pres

sN

utr

itio

nan

dM

etab

olis

min

Car

diov

ascu

lar

Dis

ease

[60]

Un

hea

lthy

diet

ary

patt

ern

sas

soci

ated

wit

hin

flam

mat

ion

and

endo

thel

iald

ysfu

nct

ion

inty

pe1

diab

etes

:Th

eE

UR

OD

IAB

stu

dy

Clin

ical

tria

lTo

inve

stig

ate

the

asso

ciat

ion

betw

een

nu

trie

nt

con

sum

ptio

nan

dbi

omar

kers

ofen

doth

elia

ldys

fun

ctio

n(E

D)

and

low

-gra

dein

flam

mat

ion

(LG

I)in

subj

ects

wit

hty

pe1

diab

etes

(n=

491)

Ah

ealt

hydi

eth

asbe

enin

vers

ely

asso

ciat

edw

ith

ED

and

LGI

Nu

trie

nt

con

sum

ptio

nan

dlif

esty

leri

skfa

ctor

sw

ere

mea

sure

din

1989

and

1997

Bio

mar

kers

ofE

Dan

dLG

I(C

-rea

ctiv

epr

otei

n,

inte

rleu

kin

6,an

dtu

mou

rn

ecro

sis

fact

orα

)w

ere

mea

sure

din

Con

sum

ptio

nof

less

fibr

e,po

lyu

nsa

tura

ted

fat

and

vege

tabl

epr

otei

n,a

nd

mor

ech

oles

tero

love

rth

est

udy

per

iod

was

asso

ciat

edw

ith

mor

eE

Dan

dLG

I

Follo

win

gdi

etar

ygu

idel

ines

inty

pe

1di

abet

esm

ayre

duce

card

iova

scu

lar

dise

ase

risk

byfa

vou

rabl

yaff

ecti

ng

ED

and

LGI

Page 12: PrescribingOptimalNutritionandPhysicalActivityas “First-Line ... · 2017-01-11 · field report a lack of efficacy of current treatments and associated adverse effects [6], ...

12 Arthritis

Ta

ble

2:C

onti

nu

ed.

1997

and

aver

aged

into

Z-s

core

s.T

he

nu

trie

nt

resi

dual

met

hod

was

use

dto

adju

stin

divi

dual

nu

trie

nt

inta

kefo

ren

ergy

inta

keFi

brom

yalg

ia

Kad

etoff

etal

.,20

12Jo

urn

alof

Neu

roim

mu

nol

ogy

[61]

Evid

ence

ofce

ntr

alin

flam

mat

ion

infi

brom

yalg

ia-i

ncr

ease

dce

rebr

ospi

nal

flu

idin

terl

euki

n-8

leve

ls

Clin

ical

tria

lSu

bjec

ts:p

atie

nts

wit

hFM

Toas

sess

intr

ath

ecal

con

cen

trat

ion

sof

pro-

infl

amm

ator

ysu

bsta

nce

sin

pati

ents

wit

hFM

Ele

vate

dce

rebr

ospi

nal

flu

idan

dse

rum

con

cen

trat

ion

sof

inte

rleu

kin

-8,b

ut

not

inte

rleu

kin

-1be

ta,i

nFM

pati

ents

Fin

din

gsco

nsi

sten

tw

ith

ace

ntr

alpr

o-in

flam

mat

ory

com

pon

ent

Ort

ega

etal

.201

2Jo

urn

alof

Med

ical

Scie

nce

and

Spor

ts[6

2]

Aqu

atic

exer

cise

impr

oves

the

mon

ocyt

epr

o-an

dan

ti-i

nfl

amm

ator

ycy

toki

ne

prod

uct

ion

bala

nce

inpa

tien

tsw

ith

fibr

omya

lgia

(FM

)

Clin

ical

tria

lSu

bjec

ts:w

omen

pati

ents

wit

hFM

and

age-

mat

ched

con

trol

grou

pof

hea

lthy

wom

en

Eval

uat

edth

eeff

ect

ofa

pool

-aqu

atic

exer

cise

prog

ram

(8m

onth

s,tw

ow

eekl

y60

min

sess

ion

s)on

the

infl

amm

ator

ycy

toki

ne

prod

uct

ion

byis

olat

edm

onoc

ytes

,an

don

the

seru

mco

nce

ntr

atio

nof

C-r

eact

ive

prot

ein

(CR

P)

Mon

ocyt

esfr

omFM

pati

ents

rele

ased

mor

ein

flam

mat

ory

cyto

kin

esth

anth

ose

from

wom

enin

con

trol

grou

pFM

wom

enh

adh

igh

circ

ula

tin

gco

nce

ntr

atio

ns

ofC

RP

Incr

ease

dIL

-6w

ith

aco

nco

mit

ant

decr

ease

dT

NFα

spon

tan

eou

sre

leas

ew

asfo

un

daf

ter

4m

onth

sA

nti

-in

flam

mat

ory

effec

tof

the

exer

cise

prog

ram

was

also

corr

obor

ated

bya

decr

ease

inth

eci

rcu

lati

ng

CR

Pco

nce

ntr

atio

n

FMis

asso

ciat

edw

ith

chro

nic

infl

amm

atio

nth

atca

nbe

offse

tw

ith

phys

ical

exer

cise

such

asaq

uat

icex

erci

seE

xerc

ise

also

impr

oved

the

hea

lth

-rel

ated

qual

ity

oflif

eof

the

FMpa

tien

ts

Hyp

erte

nsi

on

Ber

nie

tal

.,20

12Jo

urn

alof

Hu

man

Hyp

erte

nsi

on[6

3]

Ren

alre

sist

ive

inde

xan

dlo

w-g

rade

infl

amm

atio

nin

pati

ents

wit

hes

sen

tial

hyp

erte

nsi

on

Clin

ical

tria

lSu

bjec

ts:h

yper

ten

sive

pati

ents

(n=

85;5

7±

14ye

ars,

61m

ales

)w

ith

out

diab

etes

,ren

al

Tost

udy

the

rela

tion

ship

betw

een

RR

Ian

dse

rum

hsC

RP

inhy

per

ten

sive

sw

ith

pres

erve

dre

nal

fun

ctio

n,w

ith

out

Pati

ents

wit

hpa

thol

ogic

RR

I(n=

21)

wer

eol

der

and

had

hig

her

hsC

RP

leve

lsco

mpa

red

wit

hpa

tien

tsw

ith

nor

mal

RR

I,as

wel

las

pati

ents

HsC

RP

isa

pred

icto

rof

both

path

olog

icR

RI

and

decr

ease

dR

V/R

RI,

even

afte

rad

just

men

tIn

esse

nti

alhy

per

ten

sion

,

Page 13: PrescribingOptimalNutritionandPhysicalActivityas “First-Line ... · 2017-01-11 · field report a lack of efficacy of current treatments and associated adverse effects [6], ...

Arthritis 13

Ta

ble

2:C

onti

nu

ed.

failu

re,

mic

roal

bum

inu

ria,

orm

ajor

infl

amm

ator

ydi

seas

e

mic

roal

bum

inu

ria

wit

hde

crea

sed

RV

/RR

I(n=

43)

HsC

RP

was

dire

ctly

rela

ted

wit

hR

RI

and

inve

rsel

yw

ith

RV

/RR

I

low

-gra

dein

flam

mat

ion

isas

soci

ated

wit

htu

bulo

inte

rsti

tial

dam

age

He

etal

.,20

12Jo

urn

alof

Hyp

erte

nsi

on[6

4]

Met

form

in-b

ased

trea

tmen

tfo

rob

esit

y-re

late

dhy

per

ten

sion

:ara

ndo

miz

ed,

dou

ble-

blin

d,pl

aceb

o-co

ntr

olle

dtr

ial

Ran

dom

ized

,do

ubl

e-bl

ind,

plac

ebo-

con

trol

led

tria

lSu

bjec

ts:p

arti

cipa

nts

ran

dom

ized

tom

etfo

rmin

(n=

180)

and

part

icip

ants

ran

dom

ized

topl

aceb

o(n=

180)

Toex

plor

ew

het

her

met

form

in-b

ased

trea

tmen

t(w

hic

hre

duce

sw

eigh

tan

din

flam

mat

ion

indi

abet

es)

ben

efits

obes

ity-

rela

ted

hyp

erte

nsi

onw

ith

out

diab

etes

24w

eek

dru

gtr

ial

Met

form

inco

mpa

red

wit

hpl

aceb

odi

dn

oth

ave

effec

tson

bloo

dpr

essu

re,b

lood

glu

cose

,an

dh

igh

-den

sity

orlo

w-d

ensi

tylip

opro

tein

chol

este

rol,

but

itdi

dre

duce

tota

lser

um

chol

este

rol

Met

form

inre

duce

dw

eigh

t,B

MI,

wai

stci

rcu

mfe

ren

cean

dbo

thsu

bcu

tan

eou

san

dvi

scer

alad

ipos

ity

and

low

ered

seru

mh

igh

-sen

siti

vity

C-r

eact

ive

prot

ein

Res

ult

ssu

ppor

ted

anin

flam

mat

ory

com

pon

ent

ofhy

pert

ensi

onin

pati

ent

wh

oar

eob

ese,

that

was

amen

able

tom

etfo

rmin

that

targ

ets

infl

amm

atio

n

Sari

etal

.201

1C

linic

alE

xper

imen

tal

Hyp

eten

sion

[65]

Th

eeff

ect

ofqu

inap

ril

trea

tmen

ton

insu

linre

sist

ance

,lep

tin

and

hig

hse

nsi

tive

C-r

eact

ive

prot

ein

inhy

per

ten

sive

pati

ents

Clin

ical

tria

lSu

bjec

ts:h

yper

ten

sive

pati

ents

(n=

54)

and

con

trol

subj

ects

(n=

24)

Toev

alu

ate

the

effec

tof

quin

apri

lon

HO

MA

-IR

,h

igh

sen

siti

veC

-rea

ctiv

epr

otei

n,a

nd

lept

inB

lood

pres

sure

,lep

tin

,hig

hse

nsi

tive

C-r

eact

ive

prot

ein

,an

dH

OM

A-I

Rw

ere

dete

rmin

edat

base

line

and

afte

r3

mon

ths

ofqu

inap

ril

trea

tmen

t

Aft

ertr

eatm

ent

wit

hqu

inap

rilH

OM

A-I

R,

hig

hse

nsi

tive

C-r

eact

ive

prot

ein

,an

dle

ptin

wer

ede

crea

sed

inhy

per

ten

sive

pati

ents

Qu

inap

rilm

aybe

use

das

ath

erap

yfo

rim

prov

ing

bloo

dpr

essu

reas

wel

las

the

insu

linre

sist

ant,

hyp

erle

ptin

emic

,an

dlo

w-g

rade

infl

amm

ator

yst

ate

inhy

per

ten

sion

Sugi

ura

etal

.201

1Jo

urn

alof

Clin

ical

Lipi

dolo

gy[6

6]

Impa

ctof

lipid

profi

lean

dh

igh

bloo

dpr

essu

reon

endo

thel

iald

amag

e

Clin

ical

tria

lJa

pan

ese

mal

eou

tpat

ien

tsw

ith

grad

eI

orII

hyp

erte

nsi

on,

Blo

odw

assa

mpl

edfo

rla

bora

tory

anal

ysis

and

endo

thel

ial

Tota

lch

oles

tero

lto

hig

h-d

ensi

tylip

opro

tein

chol

este

rolr

atio

Impa

ired

endo

thel

ial

fun

ctio

nw

asas

soci

ated

wit

hin

crea

sed

Page 14: PrescribingOptimalNutritionandPhysicalActivityas “First-Line ... · 2017-01-11 · field report a lack of efficacy of current treatments and associated adverse effects [6], ...

14 Arthritis

Ta

ble

2:C

onti

nu

ed.

alon

gw

ith

gen

der

and

age-

mat

ched

nor

mot

ensi

vesu

bjec

ts(b

othn=

25)

fun

ctio

nw

asas

sess

edby

flow

-med

iate

ddi

lati

on(F

MD

)

(tot

al-C

/HD

L-C

)w

asin

vers

ely

corr

elat

edw

ith

the

FMD

valu

ean

dpo

siti

vely

corr

elat

edw

ith

both

mal

ondi

alde

hyde

-m

odifi

edlo

w-d

ensi

tylip

opro

tein

and

hig

h-s

ensi

tivi

tyC

-rea

ctiv

epr

otei

nva

lues

toth

ose

inn

orm

oten

sive

subj

ects

wit

hh

igh

tota

l-C

/HD

L-C

tota

l-C

/HD

L-C

valu

es,

poss

ibly

asa

resu

ltof

incr

ease

dva

scu

lar

oxid

ativ

est

ress

and

infl

amm

atio

nIn

earl

yst

ages

ofat

her

oscl

eros

is,t

he

impa

ctof

both

tota

l-C

/HD

L-C

and

BP

may

besi

mila

rin

term

sof

endo

thel

iald

amag

e

Insu

linre

sist

ance

/met

abol

icsy

ndr

ome

Piy

aet

al.,

2006

inpr

ess

Jou

rnal

ofE

ndo

crin

olog

y[6

7]

Adi

poki

ne

infl

amm

atio

nan

din

sulin

resi

stan

ce:

the

role

ofgl

uco

se,l

ipid

san

den

doto

xin

Rev

iew

Toex

amin

eim

pact

ofn

utr

ien

tssu

chas

glu

cose

and

lipid

son

infl

amm

ator

ypa

thw

ays,

spec

ifica

llyw

ith

inad

ipos

eti

ssu

e,an

dh

owth

ese

infl

uen

cead

ipok

ine

infl

amm

atio

nan

din

sulin

resi

stan

ceSe

arch

stra

tegy

un

spec

ified

Th

rou

ghov

ern

utr

itio

n,

glu

cose

,lip

ids,

and

endo

toxi

naff

ect

diff

eren

tti

ssu

esto

med

iate

anab

erra

nt

infl

amm

ator

yre

spon

sean

dau

gmen

tpa

thog

enes

isof

insu

linre

sist

ance

and

met

abol

icdi

seas

e

Evid

ence

supp

orts

the

pers

iste

nt

insu

lts

from

dysf

un

ctio

nal

diet

sth

atn

eed

tobe

the

targ

ets

ofin

terv

enti

onR

edu

cin

gth

ebu

rden

inth

isw

aym

ayim

pact

peo

ple’

slo

ng-

term

hea

lth

Shoe

lson

etal

.,20

06Jo

urn

alof

Clin

ical

Inve

stig

atio

n[6

8]

Infl

amm

atio

nan

din

sulin

resi

stan

ceR

evie

w

Evid

ence

has

linke

din

flam

mat

ion

toth

epa

thog

enes

isof

type

2di

abet

es(T

2D)

Sear

chst

rate

gyu

nsp

ecifi

ed

Wit

hdi

scov

ery

ofan

impo

rtan

tro

lefo

rti

ssu

em

acro

phag

es,t

hes

efi

ndi

ngs

are

hel

pin

gto

resh

ape

thin

kin

gab

out

how

obes

ity

incr

ease

sth

eri

skfo

rT

2Dan

dm

etab

olic

syn

drom

e

Th

eev

olvi

ng

con

cept

ofin

sulin

resi

stan

cean

dT

2Das

hav

ing

imm

un

olog

ical

com

pon

ents

and

asim

prov

ing

the

pict

ure

ofh

owin

flam

mat

ion

mod

ula

tes

met

abol

ism

prov

ides

new

oppo

rtu

nit

ies

for

usi

ng

anti

-in

flam

mat

ory

stra

tegi

esto

addr

ess

met

abol

icco

nse

quen

ces

ofex

cess

adip

osit

y

Page 15: PrescribingOptimalNutritionandPhysicalActivityas “First-Line ... · 2017-01-11 · field report a lack of efficacy of current treatments and associated adverse effects [6], ...

Arthritis 15

Ta

ble

2:C

onti

nu

ed.

Isch

emic

hea

rtdi

seas

e

Sim

on,2

012

Cir

cula

tion

Jou

rnal

[69]

Infl

amm

atio

nan

dva

scu

lar

inju

ryR

evie

w

Toex

amin

eth

ece

ntr

alro

leof

infl

amm

atio

nin

vasc

ula

rin

jury

and

repa

irSe

arch

stra

tegy

un

spec

ified

Bin

din

gsi

tefo

rG

PIbα

inM

ac-1

show

sth

atle

uko

cyte

enga

gem

ent

ofpl

atel

etG

PIbα

via

Mac

-1is

crit

ical

for

the

biol

ogic

alre

spon

seto

vasc

ula

rin

jury

,th

rom

bosi

s,va

scu

litis

,gl

omer

ulo

nep

hri

tis,

and

mu

ltip

lesc

lero

sis

Alm

ost

alli

nfl

amm

atio

nis

plat

elet

depe

nde

nt

Lig

and

enga

gem

ent

ofM

ac-1

init

iate

sa

nov

elge

ne

that

prom

otes

infl

amm

atio

n

Kal

oger

opou

los

etal

.,20

12H

eart

Failu

reC

linic

s[7

0]

From

risk

fact

ors

tost

ruct

ura

lhea

rtdi

seas

e:th

ero

leof

infl

amm

atio

nR

evie

wR

evie

wst

rate

gyu

nsp

ecifi

ed

Ele

vate

dle

vels

ofci

rcu

lati

ng

proi

nfl

amm

ator

ycy

toki

nes

and

adip

okin

esh

ave

been

rep

eate

dly

asso

ciat

edw

ith

incr

ease

dri

skfo

rcl

inic

ally

man

ifes

t(S

tage

C)

hea

rtfa

ilure

inla

rge

coh

ort

stu

dies

.Th

ero

leof

low

-gra

de,s

ubc

linic

alin

flam

mat

ory

acti

vity

inth

etr

ansi

tion

from

risk

fact

ors

(Sta

geA

hea

rtfa

ilure

)to

stru

ctu

ral

hea

rtdi

seas

e(S

tage

Bh

eart

failu

re)

isle

ssw

ell

un

ders

tood

Rec

ent

evid

ence

sugg

ests

that

chro

nic

low

-gra

dein

flam

mat

ory

acti

vity

isin

volv

edin

mos

tm

ech

anis

ms

un

derl

yin

gpr

ogre

ssio

nof

stru

ctu

ral

hea

rtdi

seas

e,in

clu

din

gve

ntr

icu

lar

rem

odel

ing

afte

ris

chem

icin

jury

,re

spon

seto

pres

sure

and

volu

me

over

load

,an

dm

yoca

rdia

lfibr

osis

Infl

amm

atio

nal

soco

ntr

ibu

tes

topr

ogre

ssio

nof

per

iph

eral

vasc

ula

rch

ange

s

Viz

zard

iet

al.2

011

Pan

min

erva

Med

ica

[71]

Hel

icob

acto

rpy

lori

and

isch

emic

hea

rtdi

seas

eR

evie

w

Man

yst

udi

esh

ave

been

perf

orm

edon

the

rela

tion

ship

betw

een

infe

ctio

nfr

omH

elic

obac

ter

pylo

rian

dat

her

oscl

erot

icdi

seas

es,l

ike

stro

kean

dis

chem

ich

eart

dise

ase

Rev

iew

ofth

elit

erat

ure

that

has

inve

stig

ated

the

role

ofH

Pin

the

deve

lopm

ent

and

path

ogen

esis

ofC

AD

.In

fect

ion

cou

ldle

adto

IHD

thro

ugh

path

way

ssu

chas

endo

thel

ialc

ells

Res

ult

sfr

omth

ese

stu

dies

hav

era

ised

new

per

spec

tive

son

coro

nar

yh

eart

dise

ase,

esp

ecia

llyre

gard

ing

the

pos

sibi

lity

ofm

odif

yin

gth

ecl

inic

alh

isto

ryof

the

dise

ase

thro

ugh

erad

icat

ion

ofth

ese

Page 16: PrescribingOptimalNutritionandPhysicalActivityas “First-Line ... · 2017-01-11 · field report a lack of efficacy of current treatments and associated adverse effects [6], ...

16 Arthritis

Ta

ble

2:C

onti

nu

ed.

Som

ein

fect

ion

sco

uld

hav

ea

role

onth

ege

nes

isan

dde

velo

pmen

tof

dam

age

toth

eva

scu

lar

wal

lan

dof

ath

erom

atou

spl

aqu

eH

Pco

uld

infl

uen

ceth

ede

velo

pmen

tof

IHD

thro

ugh

vari

ous

path

way

sSe

arch

stra

tegy

un

spec

ified

colo

niz

atio

n,c

han

ges

inth

elip

idpr

ofile

s,in

crea

sed

coag

ula

tion

and

plat

elet

aggr

egat

ion

leve

ls,i

ndu

ctio

nof

mol

ecu

lar

mim

icry

mec

han

ism

s,an

dth

epr

omot

ion

ofa

low

-gra

desy

stem

icin

flam

mat

ion

infe

ctiv

em

icro

orga

nis

ms

Furt

her

stu

dies

indi

cate

d

Kid

ney

dise

ase

Kan

get

al.,

2012

Jou

rnal

ofK

orea

nM

edic

alSc

ien

ce[7

2]

Low

-gra

dein

flam

mat

ion

,met

abol

icsy

ndr

ome

and

the

risk

ofch

ron

icki

dney

dise

ase:

a20

05K

orea

nN

atio

nal

Hea

lth

and

Nu

trit

ion

Exa

min

atio

nSu

rvey

Cro

ss-s

ecti

onal

stu

dySu

bjec

ts:a

dult

sre

gist

ered

inth

en

atio

nal

surv

ey(n=

5291

)

Toex

amin

eth

ere

lati

onsh

ipbe

twee

nw

hit

ebl

ood

cell

(WB

C)

cou

nt

and

chro

nic

kidn

eydi

seas

e≥s

tage

3M

easu

res

ofgl

omer

ula

rfi

ltra

tion

rate

s

Low

-gra

dein

flam

mat

ion

isas

soci

ated

wit

hch

ron

icki

dney

dise

ase

inp

eopl

ew

ith

met

abol

icsy

ndr

ome≥s

tage

3

Low

-gra

dein

flam

mat

ion

asso

ciat

edw

ith

chro

nic

kidn

eydi

seas

e≥s

tage

3in

peo

ple

wit

hm

etab

olic

syn

drom

esu

gges

tsn

ewtr

eatm

ent

appr

oach

es

Koc

yigi

tet

al.,

2012

Am

eric

anJo

urn

alof

Nep

hro

logy

[73]

Ear

lyar

teri

alst

iffn

ess

and

infl

amm

ator

ybi

o-m

arke

rsin

nor

mot

ensi

vepo

lycy

stic

kidn

eydi

seas

epa

tien

ts

Clin

ical

tria

lC

ross

-sec

tion

alde

sign

Pati

ents

(n=

50)

wit

hau

toso

mal

-dom

inan

tki

dney

dise

ase

(AD

PK

D)

(42%

mal

es,3

6.6±

9.9

year

s,n

obl

ood

pres

sure

med

icat

ion

)an

dh

ealt

hyco

ntr

ols

(n=

50)

(44%

mal

es,3

5.4±

6.4

year

s)

Tocl

arif

yte

mpo

ral

rela

tion

ship

betw

een

AD

PK

D,h

yper

ten

sion

,an

dth

elo

ssof

ren

alfu

nct

ion

,pa

tien

tsw

ith

earl

y-st

age

AD

PK

Dw

ho

did

not

yet

hav

ehy

pert

ensi

onw

ere

exam

ined

Pu

lse

wav

eve

loci

ty(P

WV

),ca

rdia

cm

orph

olog

yan

dfu

nct

ion

,aor

tic

elas

tic

inde

xes,

esti

mat

edgl

omer

ula

rfi

ltra

tion

rate

(eG

FR),

24-h

our

ambu

lato

rybl

ood

pres

sure

,in

terl

euki

n-6

(IL-

6),t

um

orn

ecro

sis

fact

or-α

(TN

F-α

),an

dh

igh

lyse

nsi

tive

C-r

eact

ive

prot

ein

(hs-

CR

P)

wer

em

easu

red

Des

pite

nor

mal

bloo

dpr

essu

re,a

orti

cst

iffn

ess

inde

xan

dpu

lse

wav

eve

loci

tyva

lues

wer

ein

crea

sed

inpa

tien

tsco

mpa

red

toco

ntr

ols

Inu

niv

aria

tean

alys

is,

IL-6

,TN

F-α

,hs-

CR

P,an

deG

FRw

ere

corr

elat

edw

ith

PW

VP

WV

ispr

edic

ted

byIL

-6,T

NF-α

,an

dh

s-C

RP

Incr

ease

dar

teri

alst

iffn

ess

and

puls

ew

ave

velo

city

are

earl

ym

anif

esta

tion

sof

AD

PK

Dap

pea

rin

gbe

fore

hyp

erte

nsi

onor

redu

ced

eGFR

Th

ese

vasc

ula

rab

nor

mal

itie

sar

ere

late

dto

sign

sof

syst

emic

low

grad

ein

flam

mat

ion

Fin

din

gssu

ppor

ta

com

mon

path

ophy

siol

ogic

alm

ech

anis

map

pare

ntl

ypr

esen

tal

soin

oth

erva

scu

lar

dise

ases

Page 17: PrescribingOptimalNutritionandPhysicalActivityas “First-Line ... · 2017-01-11 · field report a lack of efficacy of current treatments and associated adverse effects [6], ...

Arthritis 17

Ta

ble

2:C

onti

nu

ed.

Luis

-R

odrı

guez

etal

.,20

12W

orld

Jou

rnal

ofD

iabe

tes

[74]

Path

ophy

siol

ogic

alro

lean

dth

erap

euti

cim

plic

atio

ns

ofin

flam

mat

ion

indi

abet

icn

eph

ropa

thy

Rev

iew

(exp

erim

enta

lan

dcl

inic

alst

udi

es)

Toid

enti

fypa

thog

enic

path

way

sfo

rea

rlie

rdi

agn

osis

and

targ

etin

gn

ovel

trea

tmen

tsSe

arch

stra

tegy

un

spec

ified

Act

ivat

ion

ofin

nat

eim

mu

nit

yw

ith

deve

lopm

ent

ofa

chro

nic

low

grad

ein

flam

mat

ory

resp

onse

isa

reco

gniz

edfa

ctor

inth

epa

thog

enes

isof

diab

etic

nep

hro

path

yE

xper

imen

tala

nd

clin

ical

stu

dies

supp

ort

vari

ous

infl

amm

ator

ym

olec

ule

san

dpa

thw

ays

inth

epa

thoe

tiol

ogy

ofdi

abet

icn

euro

path

y

Incr

ease

dkn

owle

dge

and

un

ders

tan

din

gof

infl

amm

ator

ym

ech

anis

ms

are

nee

ded

toau

gmen

tcl

inic

alin

terv

enti

ons

for

this

com

plic

atio

n

Tan

get

al.,

2012

Inte

rnat

ion

alJo

urn

alof

Nep

hro

logy

[75]

Infl

amm

atio

nan

dox

idat

ive

stre

ssin

obes

ity-

rela

ted

glom

eru

lopa

thy

Rev

iew

Tofo

cus

onin

flam

mat

ion

and

oxid

ativ

est

ress

inth

epr

ogre

ssio

nof

obes

ity-

rela

ted

glom

eru

lopa

thy

and

poss

ible

inte

rven

tion

sto

prev

ent

kidn

eyin

jury

inob

esit

ySe

arch

stra

tegy

un

spec

ified

Obe

sity

-rel

ated

glom

eru

lopa

thy

isa

maj

orca

use

ofen

d-st

age

ren

aldi

seas

e.O

besi

tyh

asbe

enco

nsi

dere

da

stat

eof

chro

nic

low

-gra

desy

stem

icin

flam

mat

ion

and

chro

nic

oxid

ativ

est

ress

Au

gmen

ted

infl

amm

atio

nin

adip

ose

and

kidn

eyti

ssu

espr

omot

esth

epr

ogre

ssio

nof

kidn

eyda

mag

ein

obes

ity

Adi

pose

tiss

ue,

wh

ich

isac

cum

ula

ted

inob

esit

y,is

ake

yen

docr

ine

orga

nth

atpr

odu

ces

mu

ltip

lebi

olog

ical

lyac

tive

mol

ecu

les,

incl

udi

ng

lept

in,a

dipo

nec

tin

,an

dre

sist

in,t

hat

affec

tin

flam

mat

ion

Oxi

dati

vest

ress

isal

soas

soci

ated

wit

hob

esit

y-re

late

dre

nal

dise

ases

and

may

trig

ger

the

init

iati

onor

prog

ress

ion

ofre

nal

dam

age

inob

esit

yB

oth

infl

amm

atio

nan

dox

idat

ive

stre

ssin

duce

dam

age

tore

nal

tubu

lean

dgl

omer

ulu

san

dre

sult

inen

doth

elia

ldy

sfu

nct

ion

inth

eki

dney

An

ti-i

nfl

amm

atio

nan

dan

tiox

idan

t

Page 18: PrescribingOptimalNutritionandPhysicalActivityas “First-Line ... · 2017-01-11 · field report a lack of efficacy of current treatments and associated adverse effects [6], ...

18 Arthritis

Ta

ble

2:C

onti

nu

ed.

inte

rven

tion

sm

aybe

ther

apie

sto

prev

ent

and

trea

tob

esit

y-re

late

dre

nal

dise

ases

Obe

sity

Hu

lsm

ans

etal

.,20

12P

LoS

On

e[7

6]

Inte

rleu

kin

-1re

cept

or-a

ssoc

iate

dki

nas

e-3

isa

key

inh

ibit

orof

infl

amm

atio

nin

obes

ity

and

met

abol

icsy

ndr

ome

Exp

erim

enta

lan

dcl

inic

alst

udi

esO

bese

indi

vidu

als

(n=

21an

d10

2)an

dag

e-m

atch

edco

ntr

ols

(n=

46)

Clu

ster

ofm

olec

ule

sw

ere

stu

died

that

supp

ort

inte

ract

ion

sbe

twee

nth

est

ress

con

diti

ons

oflo

w-g

rade

infl

amm

atio

nan

dox

idat

ive

stre

ssin

mon

ocyt

esE

ffec

tof

thre

em

onth

wei

ght

loss

afte

rba

riat

ric

surg

ery

exam

ined

Vis

cera

lobe

sity

isas

soci

ated

wit

hty

pe2

diab

etes

and

met

abol

icsy

ndr

ome

Low

-gra

dech

ron

icin

flam

mat

ion

and

oxid

ativ

est

ress

syn

ergi

zein

obes

ity

and

obes

ity-

indu

ced

diso

rder

sO

dds

rati

oof

hig

h-s

ensi

tivi

tyC

-rea

ctiv

epr

otei

n,a

wid

ely

use

dm

arke

rof

syst

emic

infl

amm

atio

n,

was

4.3

Wei

ght

loss

was

wit

ha

low

erin

gof

syst

emic

infl

amm

atio

nan

da

decr

easi

ng

nu

mbe

rof

met

abol

icsy

ndr

ome

com

pon

ents

An

incr

ease

inre

acti

veox

ygen

spec

ies

inco

mbi

nat

ion

wit

hob

esit

y-as

soci

ated

low

adip

onec

tin

and

hig

hgl

uco

sean

din

terl

euki

n-6

was

iden

tifi

edas

the

cau

seof

the

decr

ease

inIR

AK

3in

TH

P-1

cells

invi

tro

Issa

and

Gri

ffin

,201

2Pa

thob

iolo

gyof

Agi

ng

and

Age

Rel

ated

Dis

ease

s[8

]

Path

obio

logy

ofob

esit

yan

dos

teoa

rth

riti

s:in

tegr

atin

gbi

omec

han

ics

and

infl

amm

atio

n

Rev

iew

Sear

chst

rate

gyu

nsp

ecifi

ed

Path

obio

logy

ofob

esit

yan

dos

teoa

rth

riti

s(O

A)

was

exam

ined

,as

wel

las

liter

atu

reth

eu

nde

rlyi

ng

syst

emic

infl

amm

atio

n,

its

rela

tion

ship

toin

acti

vity

,an

dth

eir

inte

ract

ion

s

Infl

amm

atio

nis

cen

tral

topr

ogre

ssio

nof

the

dise

ase

cycl

ein

volv

ing

obes

ity,

oste

oart

hri

tis,

and

phys

ical

inac

tivi

tyM

etab

olic

infl

amm

atio

nis

belie

ved

toco

ntr

ibu

teto

met

abol

icin

flex

ibili

tyan

don

-goi

ng

prod

uct

ion

ofpr

o-in

flam

mat

ory

med

iato

rsFi

ndi

ngs

supp

ort

that

met

abol

icin

flam

mat

ion

incr

ease

sO

Ari

sk

Page 19: PrescribingOptimalNutritionandPhysicalActivityas “First-Line ... · 2017-01-11 · field report a lack of efficacy of current treatments and associated adverse effects [6], ...

Arthritis 19

Ta

ble

2:C

onti

nu

ed.

Ric

o-R

osill

oan

dV

ega-

Rob

ledo

,201

2R

evis

taM

edic

ade

lIn

stit

uto

Mex

ican

ode

lSe

guro

Soci

al[7

7]

New

tren

dsin

mac

roph

ages

,in

flam

mat

ion

and

adip

ose

tiss

ue

Rev

iew

Toh

igh

ligh

tth

em

acro

phag

epa

rtic

ipat

ion

inth

ege

ner

atio

nof

obes

ity-

indu

ced

infl

amm

atio

nSe

arch

stra

tegy

un

spec

ified

Acc

um

ula

tin

gev

iden

cesu

gges

tth

ein

volv

emen

tof

adip

ose

tiss

ue

deri

ved

prot

ein

s,co

llect

ivel

ykn

own

asad

ipok

ines

asw

ella

sot

her

fact

ors

prod

uce

din

this

tiss

ue

byce

llsbe

side

sad

ipoc

ytes

,lik

efi

brob

last

s,ly

mph

ocyt

es,

and

mac

roph

ages

Obe

sity

burd

enon

hea

lth

exte

nds

acro

ssm

ult

iple

orga

ns

syst

ems

and

dise

ases

(ath

eros

cler

osis

,co

ron

ary

hea

rtdi

seas

es,

oste

oart

hri

tis,

diab

etes

,hy

per

ten

sion

,an

ddy

slip

idem

ia)

Obe

sity

isco

nsi

dere

da

low

-in

flam

mat

ory

con

diti

onA

nin

crea

sin

gn

um

ber

ofre

port

ssu

gges

tth

atth

ead

ipos

eti

ssu

eit

self

mig

ht

bea

sou

rce

ofpr

o-in

flam

mat

ory

fact

ors

and

ata

rget

ofin

flam

mat

ory

proc

esse

sEv

iden

cesu

ppor

tsin

volv

emen

tof

adip

ose

tiss

ue-

deri

ved

prot

ein

s,co

llect

ivel

ykn

own

asad

ipok

ines

and

oth

erfa

ctor

spr

odu

ced

inth

isti

ssu

eby

cells

besi

des

adip

ocyt

es(fi

brob

last

s,ly

mph

ocyt

es,a

nd

mac

roph

ages

)

Stie

nst

ra,2

007

PPA

RR

esea

rch

[78]

PPA

Rs,

obes

ity,

and

infl

amm

atio

nR

evie

w

Toad

dres

sth

ero

leof

pero

xiso

me

prol

ifer

ator

-act

ivat

orre

cept

ors

(PPA

Rs)

inob

esit

y-in

duce

din

flam

mat

ion

spec

ifica

llyin

adip

ose

tiss

ue,

liver

,an

dth

eva

scu

lar

wal

lSe

arch

stra

tegy

un

spec

ified

Ch

ange

sin

infl

amm

ator

yst

atu

sof

adip

ose

tiss

ue

and

liver

wit

hob

esit

ysu

ppor

tsco

-exi

sten

tch

ron

iclo

w-l

evel

infl

amm

atio

nV

ario

us

mol

ecu

lar

mec

han

ism

sh

ave

been

impl

icat

edin

obes

ity-

indu

ced

infl

amm

atio

n(s

ome

mod

ula

ted

byP

PAR

s)P

PAR

sm

odu

late

the

infl

amm

ator

yre

spon

se,

hen

ce,c

onst

itu

tea

ther

apeu

tic

targ

etto

mit

igat

eob

esit

y-in

duce

din

flam

mat

ion

and

its

con

sequ

ence

s

Obe

sity

isac

com

pan

ied

wit

hfa

tst

orag

ein

tiss

ues

oth

erth

anad

ipos

eti

ssu

e(l

iver

and

skel

etal

mu

scle

)w

hic

hm

ayle

adto

loca

lin

sulin

resi

stan

cean

dst

imu

late

infl

amm

atio

nO

besi

tych

ange

sth

em

orph

olog

yan

dco

mpo

siti

onof

adip

ose

tiss

ue,

lead

ing

toch

ange

sin

its

prot

ein

prod

uct

ion

and

secr

etio

nin

clu

din

gpr

o-in

flam

mat

ory

med

iato

rs

Page 20: PrescribingOptimalNutritionandPhysicalActivityas “First-Line ... · 2017-01-11 · field report a lack of efficacy of current treatments and associated adverse effects [6], ...

20 Arthritis

Ta

ble

2:C

onti

nu

ed.

Tajik

etal

.201

2in

pres

sJo

urn

alof

En

docr

inol

ogic

alIn

vest

igat

ion

[79]

Eff

ect

ofdi

et-i

ndu

ced

wei

ght

loss

onin

flam

mat

ory

cyto

kin

esin

obes

ew

omen

Clin

ical

tria

lSu

bjec

ts:P

rem

enop

ausa

lob

ese

wom

en(b

ody

mas

sin

dex≥

30)

aged

21to

54ye

ars

wit

hou

tdi

abet

es,h

yper

ten

sion

,or

hype

rlip

idem

ia(n=

29)

Toev

alu

ate

chan

ges

inpr

o/an

ti-i

nfl

amm

ator

yad

ipoc

ytok

ines

and

met

abol

icpr

ofile

afte

rm

oder

ate

diet

-in

duce

dw

eigh

t,an

thro

pom

etri

cpa

ram

eter

s,lip

idan

dgl

uco

sepr

ofile

s,IL

-6,

IL-1

0,an

dIL

-18

wer

em

easu

red

Subj

ects

then

ente

red

into

aw

eigh

tre

duct

ion

prog

ram

(3m

onth

s)

Bod

ym

ass

inde

x,w

aist

circ

um

fere

nce

,tri

ceps

skin

fold

thic

knes

s,to

tal

chol

este

rol,

trig

lyce

ride

,an

dfa

stin

gpl

asm

agl

uco

sede

crea

sed,

wh

ileH

DL-

chol

este

rol

incr

ease

dW

hile

plas

ma

leve

lsof

IL-6

and

IL-1

8de

crea

sed,

no

chan

gew

asob

serv

edin

circ

ula

tin

gle

vels

ofIL

-10

Obe

sity

isas

soci

ated

wit

hlo

w-g

rade

syst

emic

infl

amm

atio

nw

hic

hh

asbe

enlin

ked

toth

ein

crea

sed

risk

ofca

rdio

vasc

ula

rdi

seas

ean

dty

pe

IIdi

abet

esin

obes

epa

tien

tsim

prov

edbo

dyco

mpo

siti

onin

duce

dby

rest

rict

ion

ofen

ergy

inta

keis

asso

ciat

edw

ith

favo

rabl

ese

rum

con

cen

trat

ion

sof

IL-6

and

IL-1

8in

obes

ew

omen

Rh

eum

atoi

dar

thri

tis

Gre

mes

ean

dFe

rrac

ciol

i20

11A

uto

imm

un

olog

yR

evie

w[8

0]

Th

em

etab

olic

syn

drom

e:th

ecr

ossr

oads

betw

een

rheu

mat

oid

arth

riti

san

dca

rdio

vasc

ula

rri

sk

Rev

iew

Rh

eum

atoi

dar

thri

tis

(RA

)pa

tien

tsh

ave

anin

cide

nce

ofca

rdio

vasc

ula

r(C

V)

dise

ases

two-

fold

that

ofth

ege

ner

alpo

pula

tion

Ath

eros

cler

osis

,th

em

ain

dete

rmin

ant

ofC

Vm

orbi

dity

and

mor

talit

y,an

dca

roti

din

tim

a-m

edia

thic

knes

s,an

earl

ypr

eclin

ical

mar

ker

ofat

her

oscl

eros

is,a

lso

occu

rea

rly

onin

RA

Sear

chst

rate

gyu

nsp

ecifi

ed

CV

risk

fact

ors

seem

toh

ave

the

sam

epr

eval

ence

inR

Aan

dn

on-R

Apa

tien

ts,t

hus

they

don

otfu

llyex

plai

nin

crea

sed

CV

burd

en,

sugg

esti

ng

that

RA

infl

amm

atio

nan

dth

erap

ies

play

aro

lein

incr

easi

ng

CV

risk

inth

ese

pati

ents

Th

em

etab

olic

syn

drom

e(M

etS)

and

fat

tiss

ue

are

likel

ym

ajor

play

ers

inth

isco

mpl

exn

etw

ork

Th

eas

soci

atio

nof

Met

San

dat

her

oscl

eros

isis

part

lym

edia

ted

byal

tere

dse

cret

ion

ofad

ipok

ines

byad

ipos

eti

ssu

ean

d,

Obe

sity

isn

owre

gard

edas

asy

stem

ic,l

ow-g

rade

infl

amm

ator

yst

ate,

and

infl

amm

atio

nas

alin

kbe

twee

nob

esit

y,m

etab

olic

syn

drom

e,an

dC

Vdi

seas

esTo

con

trol

CV

risk

,dat

asu

ppor

tth

en

eces

sity

of“t

igh

tco

ntr

ol”

ofin

flam

mat

ion

from

both

RA

and

Met

S

Page 21: PrescribingOptimalNutritionandPhysicalActivityas “First-Line ... · 2017-01-11 · field report a lack of efficacy of current treatments and associated adverse effects [6], ...

Arthritis 21

Ta

ble

2:C

onti

nu

ed.

onth

eot

her

han

d,th

ere

are

evid

ence

that

adip

okin

esm

aypl

aya

role

inin

flam

mat

ory

RA

Pre

teet

al.,

2011

Au

toim

mu

nol

ogy

Rev

iew

[81]

Ext

ra-a

rtic

ula

rm

anif

esta

tion

sof

rheu

mat

oid

arth

riti

s:A

nu

pdat

e

Rev

iew

Rh

eum

atoi

dar

thri

tis

(RA

)is

anim

mu

ne-

med

iate

ddi

seas

ein

volv

ing

chro

nic

low

-gra

dein

flam

mat

ion

that

may

prog

ress

ivel

yle

adto

join

tde

stru

ctio

n,

defo

rmit

y,di

sabi

lity,

and

even

deat

hD

espi

teit

spr

edom

inan

tos

teoa

rtic

ula

ran

dp

eria

rtic

ula

rm

anif

esta

tion

s,R

Ais

asy

stem

icdi

seas

eof

ten

asso

ciat

edw

ith

cuta

neo

us

and

orga

n-s

peci

fic

extr

a-ar

ticu

lar

man

ifes

tati

ons

(EA

M)

Cu

rren

tR

evie

ws

know

ledg

eab

out

EA

Min

term

sof

freq

uen

cy,c

linic

alas

pec

ts,a

nd

curr

ent

ther

apeu

tic

appr

oach

es.I

nan

init

iala

ttem

ptat

acl

assi

fica

tion

,we

sepa

rate

dE

AM

from

RA

co-m

orbi

diti

esan

dfr

omge

ner

al,c

onst

itu

tion

alm

anif

esta

tion

sof

syst

emic

infl

amm

atio

n.E

AM

was

clas

sifi

edas

cuta

neo

us

and

visc

eral

form

s,bo

thse

vere

and

not

seve

reSe

arch

stra

tegy

un

spec

ified

Inag

greg

ated

data

from

12la

rge

RA

coh

orts

,pa

tien

tsw

ith

EA

M,

esp

ecia

llyth

ese

vere

form

s,w

ere

fou

nd

toh

ave

grea

ter

co-m

orbi

dity

and

mor

talit

yth

anpa

tien

tsw

ith

out

EA

M

Un

ders

tan

din

gth

eco

mpl

exit

yof

EA

Man

dth

eir

man

agem

ent

rem

ain

sa

chal

len

gefo

rcl

inic

ian

s,es

peci

ally

sin

ceth

eeff

ecti

ven

ess

ofdr

ug

ther

apy

onE

AM

awai

tsst

udy

Stro

ke

Den

eset

al.2

011

Cer

ebro

vasc

ula

rD

isea

se[8

2]

Inte

rleu

kin

-1an

dst

roke

:bi

omar

ker,

har

bin

ger

ofda

mag

e,an

dth

erap

euti

cta

rget

Rev

iew

Infl

amm

atio

nis

esta

blis

hed

asa

con

trib

uto

rto

cere

brov

ascu

lar

dise

ase

Ris

kfa

ctor

sfo

rst

roke

incl

ude

man

yco

ndi

tion

sas

soci

ated

wit

hch

ron

icor

acu

tein

flam

mat

ion

,an

din

flam

mat

ory

chan

ges

inth

ebr

ain

afte

rce

rebr

ovas

cula

rev

ents

con

trib

ute

Evid

ence

supp

orts

impo

rtan

ceof

per

iph

eral

ly-d

eriv

edim

mu

ne

cells

and

infl

amm

ator

ym

olec

ule

sin

vari

ous

cen

tral

ner

vou

ssy

stem

diso

rder

s,in

clu

din

gst

roke

Infl

amm

ator

ycy

toki

ne,

inte

rleu

kin

-1(I

L-1)

,pl

ays

api

vota

lrol

ein

both

loca

lan

dsy

stem

ic

Blo

ckad

eof

IL-1

cou

ldbe

ther

apeu

tica

llyu

sefu

lin

seve

rald

isea

ses

wh

ich

are

risk

fact

ors

for

stro

keT

her

eis

con

side

rabl

epr

eclin

ical

and

clin

ical

evid

ence

that

inh

ibit

ion

ofIL

-1by

IL-1

rece

ptor

anta

gon

ist

may

beva

luab

lein

the

man

agem

ent

ofac

ute

stro

ke

Page 22: PrescribingOptimalNutritionandPhysicalActivityas “First-Line ... · 2017-01-11 · field report a lack of efficacy of current treatments and associated adverse effects [6], ...

22 Arthritis

Ta

ble

2:C

onti

nu

ed.

toou

tcom

ein

exp

erim

enta

lst

udi

es,w

ith

grow

ing

evid

ence

from

clin

ical

rese

arch

Sear

chst

rate

gyu

nsp

ecifi

ed

infl

amm

atio

nan

dis

ake

ydr

iver

ofp

erip

hera

lan

dce

ntr

alim

mu

ne

resp

onse

sto

infe

ctio

nor

inju

ry

Wu

etal

.,20

12A

mer

ican

Jou

rnal

ofR

hin

olog

ical

Alle

rgy

[83]

Ris

kof

stro

keam

ong

pati

ents

wit

hrh

inos

inu

siti

s:a

popu

lati

on-b

ased

stu

dyin

Taiw

an

Popu

lati

on-b

ased

tria

lP

rosp

ecti

veco

hor

tst

udy

Pati

ents

inTa

iwan

(Lon

gitu

din

alH

ealt

hIn

sura

nce

Dat

abas

e20

05(L

HID

2005

))w

ho

had

rece

ived

adi

agn

osis

ofrh

inos

inu

siti

s(n=

53,6

53)

betw

een

Jan

uar

y1,

2004

and

Dec

embe

r31

,200

5C

ontr

olgr

oup

(1:4

)dr

awn

from

the

sam

eda

taba

sew

asm

atch

edfo

rag

ean

dge

nde

r(n=

214,

624)

Eac

hpa

tien

tw

asfo

llow

edu

pu

sin

gda

taen

tere

du

nti

lth

een

dof

2006

Pro

port

ion

alh

azar

dre

gres

sion

sw

ere

per

form

edto

eval

uat

eth

eh

azar

dra

tios

(HR

s)af

ter

adju

stin

gfo

rpo

ten

tial

con

fou

ndi

ng

fact

ors

Pati

ents

wit

hrh

inos

inu

siti

sw

ere

mor

elik

ely

tosu

ffer

stro

kes

than

the

con

trol

popu

lati

on,a

fter

adju

stin

gfo

rp

oten

tial

con

fou

nde

rs

Bot

hac

ute

and

chro

nic

sin

usi

tis

are

risk

fact

ors

orm

arke

rsfo

rst

roke

that

isin

depe

nde

nt

oftr

adit

ion

alst

roke

risk

fact

ors

Furt

her

epid

emio

logi

cal

rese

arch

isw

arra

nte

d

Page 23: PrescribingOptimalNutritionandPhysicalActivityas “First-Line ... · 2017-01-11 · field report a lack of efficacy of current treatments and associated adverse effects [6], ...

Arthritis 23

Table 3: Pro- and anti-inflammatory foods (Source: [85–87]).

Proinflammatory foods Anti-inflammatory foods

AlcoholRegular high consumption irritates esophagus, larynx, andliver which can lead to chronic inflammation whichpromotes tumor growth at sites of chronic irritationCooking oilsA diet of high imbalance of omega-6 to omega-3 ratiopromotes inflammation (e.g., heart disease and cancer)Dairy productsMeat (commercially produced meats where animals are fedgrains such as soy beans and corns (a diet high ininflammatory omega-6 fatty acids and low inanti-inflammatory omega-3 fatty acids; also, these animalshave limited exercise and raised to gain excess fat, ending upwith high saturated fats. To make the animals grow faster andprevent them from getting sick, they are injected withhormones and fed antibiotics.)Red meats (beef, lambs and pork) and processed meats (has,sausages, and salami)Red meat contains a molecule humans do not naturallyproduce (Neu5Gc) that leads to the production of antibodiesin defense of it, an immune response that may triggerchronic inflammation, and low grade inflammation (linkedto heart disease and cancer)Refined grains devoid of fiber and vitamin B compared withunrefined grains (have bran, germs and aleurone layer),refined grains like refined sugar with high glycemic indexWhen consistently consumed hasten onset heart disease andcancerAlso often laden with fat and sugar and artificial flavors andpartially hydrogenated oilArtificial food additivesAspartame and monosodium glutamate reportedly triggerinflammatory responses (particularly in those withinflammatory conditions, for example, rheumatoid arthritisSugarsTrans fats (found in deep fried foods, commercially bakedgoods, and those prepared with partially dehydrongenatedoil, margarine, and vegetable shortening

The “anti-inflammatory” nutritional plan includes thefollowing.Avoidance of sweets and sugarAvoidance of high refined foods such as processedfoods (white bread and rice, and pasta)Minimal fats (virgin olive oil okay as it has excellentanti-inflammatory properties)High fiber foods including dark breads such as rye andpumpernickelNo alcoholRecommended anti-inflammatory foods:Oatmeal (not instant)Asparagus, avocado, beets, Brussel sprouts,broccoli, cauliflower, kale, parsnip, spinachRomaine lettuceBerriesStrawberries, blueberries, raspberries, blackberriesGreen apples, oranges, pears, lemons, cantaloupeMelonOlivesUnsalted raw nutsSunflower seedsExtra virgin olive oilWaterGreen teaBeans, chickpeas, black beansLentilsLow-fat turkey/chickenEggsSalmonLow-sodium tuna packed in waterDairyLow-fat milk products are acceptable particularly plainyogurt, cottage, and solid cheeses, if any, like Swiss orcheddar, feta

physical activity. With respect to nutrition, basic assess-ment can be done and education undertaken regardingpatients’ knowledge with the inflammatory characteristics oftheir diets and incorporating anti-inflammatory foods (seeTable 3).

In addition, in the interest of best practice, as pri-mary nonpharmacologic practitioners, contemporary phys-ical therapists are integrating into practice health educa-tion including initiating and supporting smoking cessation,improved sleep hygiene, and stress management [94]. Giventhat smoking, poor sleep, and stress are all associated withlow-grade inflammation and hyperimmune response, teammembers such as nutritionists and health counselors couldbe used to greater advantage on the health care team topromote effective health education related to health behaviorchange. In acute conditions, such education needs to beintroduced potentially with pharmacologic intervention toreduce inflammation and pain expediently. However, as

the acute episode subsides and the condition stabilizes,medication needs to be reduced as much as possible, andperhaps completely, as health living practices take maximaleffect.

The benefits of healthy living have no better beenexemplified than in an elegant but simple study reported byFord and colleagues [95]. In their study of over 23,000 peoplebetween 35 and 65 years old, they reported that over an eight-year period, people who did not smoke; had a body massindex of less than 30 kg·m2; were physically active for at least3.5 hours weekly; and ate healthily reduced their risk of type2 diabetes mellitus by 93%, myocardial infarction by 81%,stroke by 50%, and cancer by 36%. Even if not all four healthbehaviors were present, risk of developing a chronic lifestyle-related condition decreased commensurate with an increasein the number of positive lifestyle factors. Furthermore,health-related quality of life increased with the number ofhealthy lifestyle behaviors that participants reported. In the

Page 24: PrescribingOptimalNutritionandPhysicalActivityas “First-Line ... · 2017-01-11 · field report a lack of efficacy of current treatments and associated adverse effects [6], ...

24 Arthritis

process of conducting the present review of the literature,we identified no medication that was associated with suchoutcomes and such low risk of side effects, if any.

In the interest of best practice, healthy living recom-mendations need to be prescribed as uniquely for theirdirect effects on the pathoetiology of osteoarthritis, andprescribed as aggressively as first-line medications. Althoughgeneral health recommendations are important for healthpromotion and disease prevention generally, the tenets ofhealthy living need to be systematically targeted to thepatient’s signs and symptoms and prescribed accordinglyincluding long-term followup and support. Not doing sodeprives the patient of evidence-informed best practiceosteoarthritis management and care.

Consistent with healthy living as a first-line approach,patients’ health behaviors need to be assessed in a measur-able, reproducible, and standardized manner. In additionto questionnaires and self-reports, despite their limitations,inflammatory biomarkers such as C-reactive protein may beuseful to objectively measure the effects of lifestyle behaviorchange rather than simply as an index of cardiovascular anddiabetes risk [96–99].

To address the reports of health care practitioners aboutlack of knowledge and confidence to effect health behaviorchange, they have a range of evidence-based interventionsat their disposal that are not time or resource intense [100–102]. In addition, the 5’s approach of behavior change, forexample, has some evidence base and has been endorsed bythe World Health Organization [103]. Its simplicity makesit attractive to health professionals, that is, assess: evaluatebehavior change status (and progress), advise: personallyrelevant behavioral recommendations, agree: set specific col-laborative, feasible goals, assist: anticipate barriers, problem-solve solutions, and complete action plan, and arrange:schedule followup, contacts, and resources.

In the interest of best practice, lifestyle behaviors needto be systematically assessed in every patient and moni-tored across the health professions the patient is seeing.Healthy living recommendations need to be prescribed asuniquely for their direct effects on the pathoetiology ofosteoarthritis as medications are, and as aggressively if first-line management is to truly reflect evidence-based practice.Although general recommendations are important for healthpromotion and disease prevention generally, healthy livingrecommendations must be systematically targeted to thepatient’s signs and symptoms. In addition to integratingdietary and activity recommendations, smoking cessation,sleep hygiene, and stress reduction should be included inthe interest of comprehensive effective care. Not doing sodeprives the patient of best practice osteoarthritis manage-ment in relation to potential comorbidities that commonlypresent in this cohort.

5. Implications: Clinical and Research

The evidence supporting lifestyle behaviour change toaddress low-grade inflammation in people with oste-oarthritis often with coexistent lifestyle-related risk factors

and low-grade inflammatory conditions (specifically, anti-inflammatory nutritional regimens, and moderate physicalactivity) is unequivocal. The evidence is sufficiently com-pelling for related healthy living assessment and recommen-dations be a component of first-line best practice in themanagement of the signs and symptoms of people withosteoarthritis. Assessments need to include lifestyle profilesrelated to body mass index, waist girth, and waist-to-hipratio; physical activity and exercise, as well as smoking, sleeppatterns, and stress (as these three latter factors have alsobeen reported to be proinflammatory). When quantifiedin standardized ways, these profiles can serve as clinicaloutcomes to assess health behavior change interventions. Thehealth behaviour change literature has exploded over the pasttwo decades, yet health professions report lack of confidencein effecting health behavior change in their patients, andlack of resources including time [100]. Although muchneeds to be done, evidence-based interventions can bereadily integrated into the framework of clinical practice andpatient visits [101, 104], for example, brief advice, referralto others professionals, and followup). Physical therapistsare particularly well positioned for initiating and supportinghealth behavior change in that patient visits tend to beprolonged and protracted over time, elements that are criticalto effective long-term sustained health behavior change.

Studies are needed to examine the differentiating char-acteristics of those people with osteoarthritis who respondprimarily to optimal nutrition and moderate physical activ-ity, and those who do not. In addition, the elements of ananti-inflammatory nutrition regimen and moderate physicalactivity program need to be refined in terms of theirprescriptive parameters, specifically, which elements shouldbe a primary focus for which patients. Another line of studiesis needed to examine the effect of such healthy lifestylechoices that increase inflammation threshold, on the needfor medication and, if medication is indicated, how mightits potency and dosage be reduced. The interactions amonghealthy lifestyle behaviors and pharmacokinetics need to beelucidated. Given that chronic systemic low-grade inflam-mation has been reported to be a common denominator oflifestyle-related conditions, studies are needed to establishthe degree to which their risk factors and manifestations arereduced in people with chronic osteoarthritis whose first-line management includes prescribing optimal nutrition andphysical activity for their anti-inflammatory effects. Further-more, the impact of low-grade inflammation can be more farreaching than physical complaints alone, in that even healthyolder adults report poorer health commensurate with levelof inflammatory markers [105]. Lastly, all indicators supportthat the approach to chronic progressive conditions suchas osteoarthritis needs to be holistic and interprofessional[106]. Research is needed to capture the breadth of thisevidence-informed practice approach.

6. Conclusion

Based on the extant literature, exploitation of anti-in-flammatory lifestyle behavior change as “first-line” interven-tion in the management of chronic osteoarthritis could well

Page 25: PrescribingOptimalNutritionandPhysicalActivityas “First-Line ... · 2017-01-11 · field report a lack of efficacy of current treatments and associated adverse effects [6], ...

Arthritis 25

constitute best practice. Chronic low-grade inflammationthat has been reported in chronic osteoarthritis is compa-rable to other lifestyle-related conditions supporting a com-mon mechanism of action. Addressing chronic low-gradeinflammation by focussing on lifestyle factors that contributedirectly to it holds the promise of increasing a patient’sinflammatory threshold, reducing rate of disease progres-sion, reducing weight, and maximizing health by minimizinga patient’s risk or manifestations of other lifestyle-relatedconditions. Even in part, such outcomes could minimizedemands on physicians for short-term symptom reduction,and management of the patient’s comorbidity related tolifestyle-related conditions. “First-line” lifestyle interven-tions to address chronic low-grade inflammation provides aninformed cost-effective basis for the 21st century prevention,potential reversal, and management of chronic osteoarthritis.Exploitation of such “first-line” intervention, however, needsto be a goal shared and supported by all healthcare teammembers.

References

[1] L. Brosseau, G. A. Wells, P. Tugwell et al., “Ottawapanelevidence-based clinical practice guidelines for the manage-ment of osteoarthritis in adults who are obese or overweight,”Physical Therapy, vol. 91, no. 6, pp. 843–860, 2011.

[2] M. C. Hochberg, R. D. Altman, K. T. April et al., “AmericanCollege of Rheumatology 2012. Recommendations for theuse of nonpharmacologic and pharmacologic therapies inosteoarthritis of the hand, hip, and knee,” Arthritis CareResearch, vol. 64, pp. 465–474, 2012.

[3] N. E. Lane and J. M. Thompson, “Management ofosteoarthritis in the primary-care setting: an evidence- basedapproach to treatment,” American Journal of Medicine A, vol.103, no. 6, pp. 25S–30S, 1997.

[4] Osteoarthritis, “National clinical guideline for care andmanagement in adults,” The National Collaborative Cen-tre for Chronic Conditions. Royal College of Physi-cians of London, http://bookshop.rcplondon.ac.uk/contents/pub242-66a1af7e-27ae-4121-bd84-6b503c80a64e.pdf, 2008.

[5] W. Zhang, G. Nuki, R. W. Moskowitz et al., “OARSI recom-mendations for the management of hip and knee osteoarthri-tis. Part III: changes in evidence following systematic cumu-lative update of research published through January 2009,”Osteoarthritis and Cartilage, vol. 18, no. 4, pp. 476–499, 2010.

[6] A. Barr and P. G. Conaghan, “Osteoarthritis: a holisticapproach,” Clinical Medicine, vol. 12, no. 2, pp. 153–155,2012.

[7] N. Hairon, “New guidance on osteoarthritis focuses onpatient education,” Nursing times, vol. 104, no. 10, pp. 21–22,2008.

[8] R. I. Issa and T. M. Griffin, “Pathobiology of obesity andosteoarthritis: integrating biomechanics and inflammation,”Pathobiology of Aging and Age Related Diseases, vol. 2012,Article ID 17470, 2 pages, 2012.

[9] D. L. Cecil, K. Johnson, J. Rediske, M. Lotz, A. M. Schmidt,and R. Terkeltaub, “Inflammation-induced chondrocytehypertrophy is driven by receptor for advanced glycation endproducts,” Journal of Immunology, vol. 175, no. 12, pp. 8296–8302, 2005.

[10] J. Rojas-Rodrıguez, L. E. Escobar-Linares, M. Garcia-Carrasco, R. O. Escarcega, S. Fuentes-Alexandro, and A.

Zamora-Ustaran, “The relationship between the metabolicsyndrome and energy-utilization deficit in the pathogenesisof obesity-induced osteoarthritis,” Medical Hypotheses, vol.69, no. 4, pp. 860–868, 2007.

[11] N. Schlesinger and R. G. Thiele, “The pathogenesis of boneerosions in gouty arthritis,” Annals of the Rheumatic Diseases,vol. 69, no. 11, pp. 1907–1912, 2010.

[12] M. D. Smith, S. Triantafillou, A. Parker, P. P. Youssef, and M.Coleman, “Synovial membrane inflammation and cytokineproduction in patients with early osteoarthritis,” Journal ofRheumatology, vol. 24, no. 2, pp. 365–371, 1997.

[13] E. Dean, S. Al-Obaidi, A. D. de Andrade et al., “The firstphysical therapy summit on global health: implications andrecommendations for the 21st century,” Physiotherapy Theoryand Practice, vol. 27, no. 8, pp. 531–547, 2011.

[14] World Health Organization, Chronic Diseases, http://www.who.int/topics/chronic diseases/en/, 2005.

[15] P. Carrera-Bastos, M. Fontes-Villalba, J. H. O. Keefe, S.Lindeberg, and L. Cordain, “The western diet and lifestyleand diseases of civilization,” Research Reports in ClinicalCardiology, vol. 2, pp. 15–35, 2012.

[16] B. Caballero, “Obesity as a consequence of undernutrition,”Journal of Pediatrics, vol. 149, no. 3, pp. S97–S99, 2006.

[17] G. Engstrom, M. Gerhardsson de Verdier, J. Rollof, P. M.Nilsson, and L. S. Lohmander, “C-reactive protein, metabolicsyndrome and incidence of severe hip and knee osteoarthri-tis. A population-based cohort study,” Osteoarthritis andCartilage, vol. 17, no. 2, pp. 168–173, 2009.

[18] L. Landaeta-Dıaz, J. M. Fernandez, M. Da Silva-Grigoletto etal., “Mediterranean diet, moderate-to-high intensitytrainingand health-related quality of life in adults with metabolicsyndrome,” European Journal of Preventive Cardiology. Inpress.

[19] T. C. Campbell, “A study on diet, nutrition and disease in thePeople’s Republic of China. Part I,” Boletin de la AsociacionMedica de Puerto Rico, vol. 82, no. 3, pp. 132–134, 1990.

[20] T. C. Campbell and C. Junshi, “Diet and chronic degenerativediseases: perspectives from China,” American Journal ofClinical Nutrition, vol. 59, supplement 1, pp. 1153S–1153S,1994.

[21] T. C. Campbell and T. M. Campbell, The China Study,Benbella Books, Dallas, Tex, USA, 2006.

[22] T. C. Campbell, B. Parpia, and J. Chen, “Diet, lifestyle, andthe etiology of coronary artery disease: the Cornell ChinaStudy,” American Journal of Cardiology B, vol. 82, no. 10, pp.18T–21T, 1998.

[23] S. Gregersen, D. Samocha-Bonet, L. K. Heilbronn, and L. V.Campbell, “Inflammatory and oxidative stress responses tohigh-carbohydrate and high-fat meals in healthy humans,”Journal of Nutrition and Metabolism, vol. 2012, Article ID238056, 8 pages, 2012.

[24] B. J. Nicklas, W. Ambrosius, S. P. Messier et al., “Diet-induced weight loss, exercise, and chronic inflammation inolder, obese adults: a randomized controlled clinical trial,”American Journal of Clinical Nutrition, vol. 79, no. 4, pp. 544–551, 2004.

[25] M. A. Allison, N. E. Jensky, S. J. Marshall, A. G. Bertoni, andM. Cushman, “Sedentary behavior and adiposity-associatedinflammation: the multi-ethnic study of atherosclerosis,”American Journal of Preventive Medicine, vol. 42, no. 1, pp.8–13, 2012.

[26] M. Gleeson, N. C. Bishop, D. J. Stensel, M. R. Lindley, S. S.Mastana, and M. A. Nimmo, “The anti-inflammatory effectsof exercise: mechanisms and implications for the prevention

Page 26: PrescribingOptimalNutritionandPhysicalActivityas “First-Line ... · 2017-01-11 · field report a lack of efficacy of current treatments and associated adverse effects [6], ...

26 Arthritis

and treatment of disease,” Nature Reviews Immunology, vol.11, no. 9, pp. 607–615, 2011.

[27] A. M. W. Petersen and B. K. Pedersen, “The anti-inflam-matory effect of exercise,” Journal of Applied Physiology, vol.98, no. 4, pp. 1154–1162, 2005.

[28] Exercise helps ease arthritis pain and stiffness, http://www.mayoclinic.com/health/arthritis/AR00009, 2012.

[29] N. P. Walsh, M. Gleeson, R. J. Shephard et al., “Positionstatement. Part one: immune function and exercise,” ExerciseImmunology Review, vol. 17, pp. 6–63, 2011.

[30] M. Gurevich, P. M. Kohn, and C. Davis, “Exercise-inducedanalgesia and the role of reactivity in pain sensitivity,” Journalof Sports Sciences, vol. 12, no. 6, pp. 549–559, 1994.

[31] R. B. Singh, G. Dubnov, M. A. Niaz et al., “Effect of an Indo-Mediterranean diet on progression of coronary artery diseasein high risk patients (Indo-Mediterranean Diet Heart Study):a randomised single-blind trial,” The Lancet, vol. 360, no.9344, pp. 1455–1461, 2002.

[32] J. Lee, V. Taneja, and R. Vassallo, “Cigarette smoking andinflammation cellular and molecular mechanisms,” Journalof Dental Research, vol. 91, no. 2, pp. 142–149, 2012.

[33] R. B. Goncalves, R. D. Coletta, K. G. Silverio et al.,“Impact of smoking on inflammation: overview of molecularmechanisms,” Inflammation Research, vol. 60, no. 5, pp. 409–424, 2011.

[34] A. Bakhru and T. P. Erlinger, “Smoking cessation andcardiovascular disease risk factors: results from the thirdnational health and nutrition examination survey,” PLoSMedicine, vol. 2, no. 6, pp. 0528–0536, 2005.

[35] Z. Baka, E. Buzas, and G. Nagy, “Rheumatoid arthritis andsmoking: putting the pieces together,” Arthritis Research &Therapy, vol. 11, no. 4, p. 238, 2009.

[36] S. Amin, J. Niu, A. Guermazi et al., “Cigarette smoking andthe risk for cartilage loss and knee pain in men with kneeosteoarthritis,” Annals of the Rheumatic Diseases, vol. 66, no.1, pp. 18–22, 2007.

[37] P. H. Black, “Stress and the inflammatory response: a reviewof neurogenic inflammation,” Brain, Behavior, and Immunity,vol. 16, no. 6, pp. 622–653, 2002.

[38] P. H. Black, “The inflammatory response is an integral part ofthe stress response: implications for atherosclerosis, insulinresistance, type II diabetes and metabolic syndrome X,”Brain, Behavior, and Immunity, vol. 17, no. 5, pp. 350–364,2003.

[39] S. Cohen, D. Janicki-Deverts, W. J. Doyle et al., “Chronicstress, glucocorticoid receptor resistance, inflammation, anddisease risk,” Proceedings of the National Academy of Science,vol. 109, no. 16, pp. 5995–5999, 2012.

[40] M. Maes, “Psychological stress and the inflammatoryresponse system,” Clinical Science, vol. 101, no. 2, pp. 193–194, 2001.

[41] T. Pedersen, “Lack of sleep, stress leads to inflammation inolder adults,” Psychology Central, http://psychcentral.com/news/2012/03/02/lack-of-sleep-stress-leads-to-inflammati-on-in-older-adults/35490.html, 2012.

[42] B. Giunta, F. Fernandez, W. V. Nikolic et al., “Inflammagingas a prodrome to Alzheimer’s disease,” Journal of Neuroin-flammation, vol. 5, p. 51, 2008.

[43] R. Veerhuis, “Histological and direct evidence for the roleof complement in the neuroinflammation of AD,” CurrentAlzheimer Research, vol. 8, no. 1, pp. 34–58, 2011.

[44] G. Candore, C. Caruso, E. Jirillo, T. Magrone, and S.Vasto, “Low grade inflammation as a common pathogeneticdenominator in age-related diseases: novel drug targets for

anti-ageing strategies and successful ageing achievement,”Current Pharmaceutical Design, vol. 16, no. 6, pp. 584–596,2010.

[45] K. T. Chou, C. C. Huang, Y. M. Chen et al., “Asthma andrisk of erectile dysfunction-A nationwide population-basedstudy,” Journal of Sexual Medicine, vol. 8, no. 6, pp. 1754–1760, 2011.

[46] A. Dixon, “The treatment of asthma in obesity,” ExpertReviews in Respiratory Medicine, vol. 6, no. 3, pp. 331–340,2012.

[47] C. T. Juel, Z. Ali, L. Nilas, and C. S. Ulrik, “Asthmaand obesity: does weight loss improve asthma control? Asystematic review,” Journal of Asthma and Allergy, vol. 5, pp.21–26, 2012.

[48] H. F. Gu, C. K. Tang, and Y. Z. Yang, “Psychological stress,immune response, and atherosclerosis,” Atherosclerosis, vol.223, no. 1, pp. 69–77, 2012.

[49] E. J. Kucharz, “Chronic inflammation-enhanced atheroscle-rosis: can we consider it as a new clinical syndrome?” MedicalHypotheses, vol. 78, no. 3, pp. 396–397, 2012.

[50] X. T. Lu, Y. F. Liu, L. Zhang et al., “Unpredictable chronicmild stress promotes atherosclerosis in high cholesterol-fedrabbits,” Psychosomatic Medicine, vol. 74, no. 6, pp. 604–611,2012.

[51] E. Ortega, R. Gilabert, I. Nunez et al., “White blood cellcount is associated with carotid and femoral atherosclerosis,”Atherosclerosis, vol. 221, no. 1, pp. 275–281, 2012.

[52] A. Pinto, D. Di Raimondo, A. Tuttolomondo, C. Butta, G.Milio, and G. Licata, “Effects of physical exercise on inflam-matory markers of atherosclerosis,” Current PharmaceuticalDesign, vol. 18, no. 28, pp. 4326–4349, 2012.

[53] P. Correa and M. B. Piazuelo, “The gastric precancerouscascade,” Journal of Digestive Diseases, vol. 13, no. 1, pp. 2–9, 2012.

[54] S. Peters, N. Grunwald, P. Rummele et al., “Chronic psy-chosocial stress increases the risk for inflammation-relatedcolon carcinogenesis in male mice,” Stress, vol. 15, no. 4, pp.403–415, 2012.

[55] L. A. Cox Jr, “Dose-response thresholds for progressivediseases,” Dose Response, vol. 10, no. 2, pp. 233–250, 2012.

[56] A. Lindberg, L. G. Larsson, E. Ronmark, and B. Lundback,“Co-morbidity in mild-to-moderate COPD: comparison tonormal and restrictive lung function,” Chronic ObstructivePulmonary Disease, vol. 8, no. 6, pp. 421–428, 2011.

[57] N. H. T. ten Hacken, “Physical inactivity and obesity: relationto asthma and chronic obstructive pulmonary disease?”Proceedings of the American Thoracic Society, vol. 6, no. 8, pp.663–667, 2009.

[58] E. F. M. Wouters, N. L. Reynaert, M. A. Dentener, and J.H. J. Vernooy, “Systemic and local inflammation in asthmaand chronic obstructive pulmonary disease is there a connec-tion?” Proceedings of the American Thoracic Society, vol. 6, no.8, pp. 638–647, 2009.

[59] C. M. Chang, C. J. Hsieh, J. C. Huang, and I. C. Huang,“Acute and chronic fluctuations in blood glucose levels canincrease oxidative stress in type 2 diabetes mellitus,” ActaDiabetologica, vol. 49, no. 1 Supplement, pp. 171–177, 2012.

[60] B. C. van Bussel, S. S. Soedamah-Muthu, R. M. Henry etal., “EURODIAB Prospective Complications Study Group,Unhealthy dietary patterns associated with inflammation andendothelial dysfunction in type 1 diabetes: The EURODIABstudy,” Nutrition and Metabolism in Cardiovascular Disease.In press.

Page 27: PrescribingOptimalNutritionandPhysicalActivityas “First-Line ... · 2017-01-11 · field report a lack of efficacy of current treatments and associated adverse effects [6], ...

Arthritis 27

[61] D. Kadetoff, J. Lampa, M. Westman, M. Andersson, and E.Kosek, “Evidence of central inflammation in fibromyalgia-increased cerebrospinal fluid interleukin-8 levels,” Journal ofNeuroimmunology, vol. 242, no. 1-2, pp. 33–38, 2012.

[62] E. Ortega, M. E. Bote, E. Giraldo, and J. J. Garcıa, “Aquaticexercise improves the monocyte pro- and anti-inflammatorycytokine production balance in fibromyalgia patients,” Scan-dinavian Journal of Medical Science and Sports, vol. 22, no. 1,pp. 104–112, 2012.

[63] A. Berni, E. Ciani, M. Bernetti et al., “Renal resistiveindex and low-grade inflammation in patients with essentialhypertension,” Journal of Human Hypertension, vol. 26, no.12, pp. 723–730, 2012.

[64] H. He, Z. Zhao, J. Chen et al., “Metformin-based treatmentfor obesity-related hypertension: a randomized, double-blind, placebo-controlled trial,” Journal of Hypertension, vol.30, no. 7, pp. 1430–1439, 2012.

[65] F. Sari, E. Eray, and R. Sari, “The effect of quinapril treatmenton insulin resistance, leptin and high sensitive C-reactiveprotein in hypertensive patients,” Clinical ExperimentalHypertension, vol. 33, no. 8, pp. 548–551, 2011.

[66] T. Sugiura, Y. Dohi, S. Yamashita et al., “Impact of lipidprofile and high blood pressure on endothelial damage,”Journal of Clinical Lipidology, vol. 5, no. 6, pp. 460–466, 2011.

[67] M. K. Piya, P. G. McTeman, and S. Kumar, “Adipokineinflammation and insulin resistance: the role of glucose,lipids and endotoxin,” Journal of Endocrinology. In press.

[68] S. E. Shoelson, J. Lee, and A. B. Goldfine, “Inflammation andinsulin resistance,” Journal of Clinical Investigation, vol. 116,no. 7, pp. 1793–1801, 2006.

[69] D. I. Simon, “Inflammation and vascular injury,” CirculationJournal, vol. 76, no. 8, pp. 1811–1818, 2012.

[70] A. P. Kalogeropoulos, V. V. Georgiopoulou, and J. Butler,“From risk factors to structural heart disease: the role ofinflammation,” Heart Fail Clinics, vol. 8, no. 1, pp. 113–123,2012.

[71] E. Vizzardi, I. Bonadei, B. Piovanelli et al., “Helicobacterpylori and ischemic heart disease,” Panminerva Medica, vol.53, no. 3, pp. 193–202, 2011.

[72] H. T. Kang, J. K. Kim, J. Y. Shim, H. R. Lee, J. A. Linton, andY. J. Lee, “Low-grade inflammation, metabolic syndrome andthe risk of chronic kidney disease: the 2005 Korean nationalhealth and nutrition examination survey,” Journal of KoreanMedical Science, vol. 27, no. 6, pp. 630–635, 2012.

[73] I. Kocyigit, M. G. Kaya, O. Orscelik et al., “Early arterialstiffness and inflammatory bio-markers in normotensivepolycystic kidney disease patients,” American Journal ofNephrology, vol. 36, no. 1, pp. 11–18, 2012.

[74] D. Luis-Rodrıguez, A. Martınez-Castelao, J. L. Gorriz, F. De-Alvaro, and J. F. Navarro-Gonzalez, “Pathophysiological roleand therapeutic implications of inflammation in diabeticnephropathy,” World Journal of Diabetes, vol. 3, no. 1, pp. 7–18, 2012.

[75] J. Tang, H. Yan, and S. Zhuang, “Inflammation and oxida-tive stress in obesity-related glomerulopathy,” InternationalJournal of Nephrology, vol. 2012, Article ID 608397, 11 pages,2012.

[76] M. Hulsmans, B. Geeraert, D. De Keyzer et al., “Interleukin-1receptor-associated kinase-3 is a key inhibitor of inflamma-tion in obesity and metabolic syndrome,” PLoS One, vol. 7,no. 1, Article ID e30414, 2012.

[77] M. G. Rico-Rosillo and G. B. Vega-Robledo, “New trendsin macrophages, inflammation and adipose tissue,” Revista

Medica del Instituto Mexicano del Seguro Social, vol. 50, no. 1,pp. 39–45, 2012.

[78] R. Stienstra, C. Duval, M. Muller, and S. Kersten, “PPARs,obesity, and inflammation,” PPAR Research, Article ID 95974,2007.

[79] N. Tajik, S. A. Keshavarz, F. Masoudkabir et al., “Effect ofdiet-induced weight loss on inflammatory cytokines in obesewomen,” Journal of Endocrinological Investigations. In press.

[80] E. Gremese and G. Ferraccioli, “The metabolic syndrome: thecrossroads between rheumatoid arthritis and cardiovascularrisk,” Autoimmunity Reviews, vol. 10, no. 10, pp. 582–589,2011.

[81] M. Prete, V. Racanelli, L. Digiglio, A. Vacca, F. Dammacco,and F. Perosa, “Extra-articular manifestations of rheumatoidarthritis: an update,” Autoimmunology Review, vol. 11, no. 2,pp. 123–131, 2011.

[82] A. Denes, E. Pinteaux, N. J. Rothwell, and S. M. Allan,“Interleukin-1 and stroke: biomarker, harbinger of damage,and therapeutic target,” Cerebrovascular Disease, vol. 32, no.6, pp. 517–527, 2011.

[83] C. W. Wu, P. Z. Chao, W. R. Hao, T. H. Liou, and H.W. Lin, “Risk of stroke among patients with rhinosinusitis:a population-based study in Taiwan,” American Journal ofRhinological Allergy, vol. 26, no. 4, pp. 278–282, 2012.

[84] A. Powell, A. J. Teichtahl, A. E. Wluka, and F. M. Cicuttini,“Obesity: a preventable risk factor for large joint osteoarthri-tis which may act through biomechanical factors,” BritishJournal of Sports Medicine, vol. 39, no. 1, pp. 4–5, 2005.

[85] L. Beck, Foods that Fight Disease. A Nutrition Guide forStaying Healthy for Life, Penguin Canada, Toronto, Canada,2010.

[86] J. Daniluk, Meals that Heal Inflammation. Embrace HealthyLiving and Eliminate Pain, One Meal at a Time, RandomHouse Canada, Toronto, Canada, 2011.

[87] A. W. Weil, Anti Inflammatory Diet and Pyramid, http://www.drweil.com/drw/u/ART02012/anti-inflammatory-diet,2012.

[88] Meeting the challenge of living well at a glance2012, Centers for Disease Control and Prevention,http://www.cdc.gov/chronicdisease/resources/publications/AAG/arthritis.htm, 2012.

[89] B. E. Wisse, “The inflammatory syndrome: the role ofadipose tissue cytokines in metabolic disorders linked toobesity,” Journal of the American Society of Nephrology, vol.15, no. 11, pp. 2792–2800, 2004.

[90] R. Liu, N. Wei, W. Guo et al., “Octreotide alleviates obesityby reducing intestinal glucose absorption and inhibiting low-grade inflammation,” European Journal of Nutrition. In press.

[91] E. Dean, “Physical therapy in the 21st century (Part II):evidence-based practice within the context of evidence-informed practice,” Physiotherapy Theory and Practice, vol.25, no. 5-6, pp. 354–368, 2009.

[92] W. Frerichs, E. Kaltenbacher, J. P. van de Leur, and E.Dean, “Can physical therapists counsel patients with lifestyle-related health conditions effectively? A systematic review andimplications,” Physiotherapy Theory and Practice, vol. 28, no.8, pp. 571–587, 2012.

[93] World Health Organization, International Classification ofFunctioning, Disability and Health, http://www.sustainable-design.ie/arch/ICIDH-2PFDec-2000.pdf, 2002.

[94] S. Hasson, “Editorial-special issue ‘physical therapy practicein the 21st century: a new evidence-informed paradigm andimplications’,” Physiotherapy Theory and Practice, vol. 25, no.5-6, pp. 327–462, 2009.

Page 28: PrescribingOptimalNutritionandPhysicalActivityas “First-Line ... · 2017-01-11 · field report a lack of efficacy of current treatments and associated adverse effects [6], ...

28 Arthritis

[95] E. S. Ford, M. M. Bergmann, J. Kroger, A. Schienkiewitz, C.Weikert, and H. Boeing, “Healthy living is the best revenge:findings from the European prospective investigation intocancer and nutrition-potsdam study,” Archives of InternalMedicine, vol. 169, no. 15, pp. 1355–1362, 2009.

[96] P. M. Ridker, “High-sensitivity C-reactive protein: potentialadjunct for global risk assessment in the primary preventionof cardiovascular disease,” Circulation, vol. 103, no. 13, pp.1813–1818, 2001.

[97] P. M. Ridker, “Clinical application of C-reactive protein forcardiovascular disease detection and prevention,” Circula-tion, vol. 107, no. 3, pp. 363–369, 2003.

[98] P. M. Ridker, M. Cushman, M. J. Stampfer, R. P. Tracy,and C. H. Hennekens, “Inflammation, aspirin, and the riskof cardiovascular disease in apparently healthy men,” NewEngland Journal of Medicine, vol. 336, no. 14, pp. 973–979,1997.

[99] P. M. Ridker, C. H. Hennekens, J. E. Buring, and N. Rifai, “C-reactive protein and other markers of inflammation in theprediction of cardiovascular disease in women,” New EnglandJournal of Medicine, vol. 342, no. 12, pp. 836–843, 2000.

[100] M. Bodner, R. E. Rhodes, W. C. Miller, and E. Dean,“Smoking cessation and counselling: practices of Canadianphysical therapists,” American Journal of Preventive Medicine,vol. 43, no. 1, pp. 67–71, 2012.

[101] E. Dean, Z. Li, W. P. Wong, and M. E. Bodner, “Cardiologybest practice-effective health education meets biomedicaladvances: reducing the ultimate knowledge translation gap,”in Novel Strategies in Ischemic Heart Disease, U. Lakshmana-doss, Ed., pp. 301–318, InTech Publishing, Rijeka, Croatia,2012.

[102] R. K. Martins and D. W. McNeil, “Review of MotivationalInterviewing in promoting health behaviors,” Clinical Psy-chology Review, vol. 29, no. 4, pp. 283–293, 2009.

[103] “The 5 A’s Cycle,” World Health Organization, http://www.who.int/diabetesactiononline/about/WHO%205A%20ppt.pdf, 2004.

[104] T. van Achterberg, G. G. J. Huisman-De Waal, N. A. B.M. Ketelaar, R. A. Oostendorp, J. E. Jacobs, and H. C.H. Wollersheim, “How to promote healthy behaviours inpatients? An overview of evidence for behaviour changetechniques,” Health Promotion International, vol. 26, no. 2,pp. 148–162, 2011.

[105] L. M. Christian, R. Glaser, K. Porter, W. B. Malarkey, D.Beversdorf, and J. K. Kiecolt-Glaser, “Poorer self-rated healthis associated with elevated inflammatory markers amongolder adults,” Psychoneuroendocrinology, vol. 36, no. 10, pp.1495–1504, 2011.

[106] A. Barr and P. G. Conaghan, “Osteoarthritis: a holisticapproach,” Clinical Medicine, vol. 12, no. 2, pp. 153–155,2012.


Excellent Long Term Safety and Efficacy · Excellent Long Term Safety and Efficacy 4 ... Biosensors International internal bench testing performed on 3.0 mm stents. Data on file

Excellent Long Term Safety and Efficacy · Excellent Long Term Safety and Efficacy 4 ... Biosensors International internal bench testing performed on 3.0 mm stents. Data on file

(Re)Engaging Novice Online Learners in an Educational Programming … · 2020-05-18 · programming, as it may have lasting effects on their views and self-efficacy towards computer

(Re)Engaging Novice Online Learners in an Educational Programming … · 2020-05-18 · programming, as it may have lasting effects on their views and self-efficacy towards computer

EstimatingDynamicEconomicModelswithFixed Effects

EstimatingDynamicEconomicModelswithFixed Effects

6 Evaluating Protective Effects of Vaccinationcourses.washington.edu/b578a/readings/bookchap6.pdf · S,λ can be estimated from either closed or open cohorts. Primary vac-cine efficacy

6 Evaluating Protective Effects of Vaccinationcourses.washington.edu/b578a/readings/bookchap6.pdf · S,λ can be estimated from either closed or open cohorts. Primary vac-cine efficacy

Memory Self-Efficacy and Beliefs about Memory …...Memory Self-Efficacy and Beliefs about Memory and Aging in Oldest-Old Adults in the Louisiana Healthy Aging Study (LHAS) Katie E.

Memory Self-Efficacy and Beliefs about Memory …...Memory Self-Efficacy and Beliefs about Memory and Aging in Oldest-Old Adults in the Louisiana Healthy Aging Study (LHAS) Katie E.

Effects of elastic foundation on the snap-through buckling ...ntur.lib.ntu.edu.tw/bitstream/246246/85611/1/11.pdf · Effects of elastic foundation on the ... to discuss the effects

Effects of elastic foundation on the snap-through buckling ...ntur.lib.ntu.edu.tw/bitstream/246246/85611/1/11.pdf · Effects of elastic foundation on the ... to discuss the effects

The Efficacy of Constructed Stream Wetland Complexes at ...€¦ · The Efficacy of Constructed Stream−Wetland Complexes at Reducing the Flux of Suspended Solids to Chesapeake Bay

The Efficacy of Constructed Stream Wetland Complexes at ...€¦ · The Efficacy of Constructed Stream−Wetland Complexes at Reducing the Flux of Suspended Solids to Chesapeake Bay

Exploring the Efficacy of Nile Red in Microplastic ...Exploring the Efficacy of Nile Red in Microplastic Quantification: A Costaining Approach Thomas Stanton,*,†, Matthew Johnson,†

Exploring the Efficacy of Nile Red in Microplastic ...Exploring the Efficacy of Nile Red in Microplastic Quantification: A Costaining Approach Thomas Stanton,*,†, Matthew Johnson,†

The Efficacy of Parochial Politics: Caste, Commitment, And Competence In

The Efficacy of Parochial Politics: Caste, Commitment, And Competence In

Short-Term Reversals and the Efficacy of Liquidity Provision

Short-Term Reversals and the Efficacy of Liquidity Provision

Reaction Mechanisms and Efficacy

Reaction Mechanisms and Efficacy

Efficacy of Chlorine Dioxide Tablets on Inactivation of ... · Efficacy of Chlorine Dioxide Tablets on Inactivation of Cryptosporidium Oocysts Jennifer L. Murphy,*,† Charles N.

Efficacy of Chlorine Dioxide Tablets on Inactivation of ... · Efficacy of Chlorine Dioxide Tablets on Inactivation of Cryptosporidium Oocysts Jennifer L. Murphy,*,† Charles N.

Tracking the effects of pulsed electro- magnetic field (PEMF ...

Tracking the effects of pulsed electro- magnetic field (PEMF ...

Understanding Collaborative Effects between the Polymer ...The collaborative effects between an applied orthogonal electrical field and the internal structure of polymer gels in

Understanding Collaborative Effects between the Polymer ...The collaborative effects between an applied orthogonal electrical field and the internal structure of polymer gels in

Improving Collective Teacher Efficacy in - Provo School · PDF fileImproving Collective Teacher Efficacy in Elementary Schools Steve Ventura Author/Consultant Corwin Professional Learning

Improving Collective Teacher Efficacy in - Provo School · PDF fileImproving Collective Teacher Efficacy in Elementary Schools Steve Ventura Author/Consultant Corwin Professional Learning

ConfirmatoryModelofMathematics Self …einspem.upm.edu.my/journal/fullpaper/vol10saugust/14... · 2016. 9. 19. · ConfirmatoryModelofMathematicsSelf-Efficacy,ProblemSolvingSkillsandPrior

ConfirmatoryModelofMathematics Self …einspem.upm.edu.my/journal/fullpaper/vol10saugust/14... · 2016. 9. 19. · ConfirmatoryModelofMathematicsSelf-Efficacy,ProblemSolvingSkillsandPrior

Neutrino conversions in hot plasma - arXiv · effects of a possible random backround magnetic field. In Section 4 we apply our general formalism to the special case of isotropic

Neutrino conversions in hot plasma - arXiv · effects of a possible random backround magnetic field. In Section 4 we apply our general formalism to the special case of isotropic

Colloidal Aggregation Affects the Efficacy of Anticancer ... · Colloidal Aggregation Affects the Efficacy of Anticancer Drugs in Cell Culture Shawn C. Owen,†,§ Allison K. Doak,‡,§

Colloidal Aggregation Affects the Efficacy of Anticancer ... · Colloidal Aggregation Affects the Efficacy of Anticancer Drugs in Cell Culture Shawn C. Owen,†,§ Allison K. Doak,‡,§

Size-Dependent Tumor Penetration and in Vivo Efficacy of ... · Size-Dependent Tumor Penetration and in Vivo Efficacy of Monodisperse Drug−Silica Nanoconjugates Li Tang,† Nathan

Size-Dependent Tumor Penetration and in Vivo Efficacy of ... · Size-Dependent Tumor Penetration and in Vivo Efficacy of Monodisperse Drug−Silica Nanoconjugates Li Tang,† Nathan

Enhanced efficacy and reduced side effects of diazepam by kava combination€¦ · ORIGINAL ARTICLE Enhanced efficacy and reduced side effects of diazepam by kava combination Rasha

Enhanced efficacy and reduced side effects of diazepam by kava combination€¦ · ORIGINAL ARTICLE Enhanced efficacy and reduced side effects of diazepam by kava combination Rasha