Vitamins and Arthritis the Roles of Vitamins A

7/25/2019 Vitamins and Arthritis the Roles of Vitamins A

1/22

Rheumatic Diseases Clinics of North America- Volume 25, Issue 2(May 1999) -

Copyright 1999 W. B. au!"ers Compa!y

315

Osteoarthritis

VITAMINS AND ARTHRITISThe Roles of Vitamins A, C, D, an !

Mar"#ran So$ers %hD

&aurie &achance M%H

#his $or% $as supporte" &y the 'ollo$i!g gra!ts I* +1-+1/0-1 I* 1341 +1 I* 6-

+-255 a!" 6u&li7 *ealth a!" gi!g #rai!i!g 8ra!t, I #02810.

epartme!t o' :pi"emiology, 3!i;ersity o' Mi7higa!, !! r&or, Mi7higa!

Address reprint requests to

Mary


2/22

+articularl" the *itamins, that contri'ute to o8iate +rocesses an 'one turno*er

that ma" 'e intrinsic to the e*elo+ment an +ro)ression of OA.

Vitamins A, C, an, ! are the ma(or antio8iants in the iet or in ietar"

su++lement +roucts that ha*e 'een ientifie as ha*in) a +otential for antio8iant

acti*it" in the +rocesses associate $ith OA. Vitamin D also ma" +la" an im+ortantrole in OA '" $a" of 'one.

31

minerali:ation an cell ifferentiation;;roles that +arallel the actions of *itamin A

an *itamin C.

There are at least four +ossi'le +ath$a"s in $hich these nutrients can influence OA2?>5?&y o=i"ati;e spe7ies. >2?>22?>?>5?

#he roles o' !utrie!ts i! the 4 pro7esses are 7omple= &e7ause o' the i!tera7ti;e systemi! $hi7h they operate. 0/?lthough me7ha!isms e=ist $ithi! the &o"y toprote7t tissues 'rom e=7essi;e o=i"ati;e a7tio!, pro"u7tio! o' +4 7a! o;er$helm those

mo"ulati!g 'a7tors. I! those i!sta!7es i! $hi7h a!a&oli7 a!" 7ata&oli7 a7ti;ities &e7ome

u!&ala!7e", tissue "amage 7a! result, espe7ially i! e=tra7ellular spa7es $here a!tio=i"a!t

e!Aymes are !ot as pre;ale!t.

Whe! 'ree ra"i7als atta7% polyu!saturate" 'atty a7i"s (63


3/22

$ith their "ou&le &o!"s, are rea"ily atta7%e" &y 'ree ra"i7als a!" o=i"iAe" to lipi"

pero=i"es, $hi7h ha;e the 7apa7ity to "amage 7ells. #he 'ree ra"i7als pro"u7e" &y lipi"

pero=i"atio!, pero=yl ra"i7als, are 7apa&le o' remo;i!g hy"roge! 'rom a"@a7e!t 'atty a7i"si"e 7hai!s, there&y propagati!g a 7hai! rea7tio! %!o$! as lipi" pero=i"atio!. si!gle

i!itiati!g e;e!t 7a! lea" to hu!"re"s o' su7h e;e!ts (0/?

#he pro"u7tio! o' 'ree ra"i7als also 7a! &e the 7o!seue!7e o' tissue "amage asso7iate"

$ith arthritis. >0?4=i"ati;e stress is &elie;e" to 7o!tri&ute to the progressio! o' arthritisrather tha! the i!itiatio! o' "isease.

31=

#i)ure 1.ipi" pero=i"atio!. +4 D rea7ti;e o=yge! spe7ies 63


4/22

With i!@ury a!" tissue "amage, mast 7ells release i!'lammatory me"iators that i!7rease

;as7ular permea&ility a!" permit 7ompleme!t a!" 7ells to e!ter tissues 'rom the

7ir7ulatio!. #he mast 7ells also promote the a7ti;ity o' polymorpho!u7lear !eutrophils(6Ms). #he a7ti;ities o' 6Ms a!" mast 7ells 7reate a! a7ute i!'lammatory respo!se

that lea"s to remo;al o' "amage" tissues a!" 7ells, tissue repair, a!" heali!g. 4!7e

ma7rophages are e!gage", there is a pote!tial 'or 'urther 7ell-me"iate" respo!sei!;ol;i!g !atural %iller (E) 7ells. #hese a7ti;ities 7a! lea" to phago7ytosis a!" 7hro!i7

i!'lammatio!.

Cho!"ro7ytes are !ormally surrou!"e" &y a! e=tra7ellular matri= (:CM) a!" a repair

pro7ess is i!itiate" $he! this matri= is remo;e". egra"atio! a!" loss o' the arti7ular7artilage matri= is a 7e!tral 'eature o' 4. #his loss o' matri= is a77ompa!ie" &y a!

i!7rease" sy!thesis o' matri= mole7ules, a pro7ess thought to &e i!;ol;e" i! matri=

repair. >0/?>09?>9?

I! the prese!7e o' lipi" pero=i"atio!, ara7hi"o!i7 a7i" 7as7a"e pro"u7ts (i.e.,

prostagla!"i!s, leu%otrie!es) release proi!'lammatory lipi" pero=i"es that may 7ause;as7ular lea%age, 7hemota=is, a!" a"here!7e

31>

o' polymorpho!u7lear leu%o7ytes. I! tur!, these may promote the ge!eratio! o' rea7ti;e

o=yge! spe7ies a!" release o' proteolyti7 e!Aymes that "egra"e 7ollage!, proteogly7a!,

a!" other 7ompo!e!ts o' the 7artilage matri=. >19?

Cellular Differentiation

Vitami! a!" ;itami! are !o$ re7og!iAe" as 'u!"ame!tal eleme!ts o' 7ellular

maturatio! a!" 7ellular "i''ere!tiatio!. +eti!oi7 a7i", a! o=i"iAe" 'orm o' ;itami! ,

regulates em&ryo!i7 "e;elopme!t a!" the "i''ere!tiatio! o' epithelial a!" mese!7hymaltissues throughout li'e. >?Vitami! has a role i! the "i''ere!tiatio! o' %erato7ytes >20?>52?

a!" mo!o7ytes i!to ma7rophages. >1?>?>1?Vitami! also appears to a7t upo! #-

lympho7ytes, $hi7h pro"u7e a ;ariety o' lympho%i!es, i!7lu"i!g the pote!t &o!e

resor&i!g age!t, osteo7last a7ti;ati!g 'a7tor. >?

Additional Biologic Actions

I!"epe!"e!t o' their prote7ti;e e''e7t o! +4 a!" mo"ulatio! o' the immu!e respo!se,these ;itami!s ha;e $ell-"es7ri&e" &iologi7 roles relate" to 4.


5/22

It is !ote$orthy that there are multiple me7ha!isms through $hi7h !utrie!ts 7a! ha;e a!

e''e7t o! either the i!itiatio! or progressio! o' 4.


6/22

#i)ure 0.Co!;ersio! o' &eta-7arote!e to reti!ol (;itami! , al"ehy"e).

relati;e amou!ts o' 7arote!oi"s "ire7tly a&sor&e" a!" meta&oliAe" to ;itami! i! thei!testi!e ;ary greatly (11?

#he +e7omme!"e" aily llo$a!7e (+) 'or ;itami! is gi;e! i! reti!ol eui;ale!ts

(+:) o' a7ti;e reti!ol (1 +: 1 mug 0.00 I3). 4!e +: o' &eta-7arote!e is mug

1 I3. #he a"ult male + 'or ;itami! is 1 +: per "ay a!" / +: per "ay 'ora! a"ult 'emale. Vitami! is 'ou!" as reti!ol i! 'oo"s su7h as li;er, egg yol%, mil%, a!"

other "airy pro"u7ts, $hereas &eta-7arote!e is 'ou!" i! "ar% gree! a!" yello$ ;egeta&les

a!" 'ruits. >11?>1?

lthough ;itami! to=i7ity is !ot 7ommo!, it 7a! o77ur $he! e=7ess amou!ts o'suppleme!ts or ma@or "ietary sour7es, su7h as li;er, are 7o!sume". &eta-7arote!e, o! the

other ha!", is rarely 7o!si"ere" to=i7, &ut 7a! a77umulate, gi;i!g the s%i! a! ora!ge-

yello$ hue.

Role of Vitamin A and Carotenoids in Oxidative tress

+e7e!t stu"ies ha;e "emo!strate" the a!tio=i"a!t 'u!7tio!s o' &eta-7arote!e a!"

7arote!oi"s, i! ge!eral, a!" their e''e7ti;e a&ility to s7a;e!ge si!glet o=yge!. >11?

Carote!oi"s are %!o$! to s7a;e!ge a!" "ea7ti;ate 'ree ra"i7als &oth i! ;itro a!" i! ;i;o.

:;i"e!7e 'rom i! ;itro e=perime!ts >1?>11?>2/?>1?suggests that &eta-7arote!e may e=ert othera!tio=i"a!t e''e7ts, i!7lu"i!g i!hi&itio! o' lipi" pero=i"atio!. Whereas some a!tio=i"a!ts

pre;e!t the i!itiatio! o' lipi" pero=i"atio!, &eta-7arote!e 7o!trols the 7hai! rea7tio!s &y

trappi!g 'ree ra"i7als, 7ompleme!ti!g the a7tio! o' other a!tio=i"a!t mole7ules.

30?

Carote!oi"s ha;e the 7apa7ity to mo"ulate the e!Aymati7 a7ti;ities o' lipo=yge!ases. >1?

Be7ause the e!" pro"u7ts o' lipo=yge!ase a7ti;ity are proi!'lammatory a!"immu!omo"ulatory mole7ules, there 7a! &e ma!y &iologi7 7o!seue!7es o' regulatio! o'

the a7ti;ity o' this e!Ayme &y 7arote!oi"s. >2/?

!other 7arote!oi", ly7ope!e, is less a&u!"a!t i! the "iet tha! &eta-7arote!e. i%e &eta-

7arote!e, ho$e;er, it is a si!glet o=yge! ue!7her a!" there'ore 7a! a7t also as a!a!tio=i"a!t. ittle "ata o! this 7arote!oi" are prese!tly a;aila&le. >2?

Vitamin A and the Immune Response

epe!"i!g upo! the parti7ular 7ompou!", "osage, a!" metho" o' a"mi!istratio!, >/?

;itami! , its pre7ursors, a!" sy!theti7 "eri;ati;es 7a! stimulate or i!hi&it ;ariousaspe7ts o' the 7ellular a!" humoral immu!e respo!se. >?
http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#F031502http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#F031502http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315011http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315011http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315011http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315011http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315011http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315011http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315061http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315061http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315061http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315011http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315011http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315011http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315010http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315010http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315010http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315011http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315011http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315011http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315028http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315028http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315028http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315061http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315061http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315061http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315010http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315010http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315010http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315028http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315028http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315028http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315027http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315027http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315027http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315078http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315078http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315078http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315076http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315076http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315076http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#F031502http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315011http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315011http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315061http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315011http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315010http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315011http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315028http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315061http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315010http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315028http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315027http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315078http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315076


7/22

&eta-7arote!e has &ee! sho$! to stimulate rat lympho7yte mitoge!esis i! ;i;o. >12?I! ;itro

stu"ies o' the a7tio!s o' &eta-7arote!e ha;e "emo!strate" that it i!7reases the !um&ers o'

huma! E 7ells a!" #-helper 7ells. >2?>?!imal stu"ies ha;e sho$! that 7arote!oi"se!ha!7e immu!e 'u!7tio! i!"epe!"e!t o' a!y pro;itami! e''e7t. >9?>1?Carote!oi"s ha;e

&ee! sho$! to e!ha!7e ma7rophage 'u!7tio!, >9?there&y mo"ulati!g the pro"u7tio! o'

rea7ti;e o=yge! spe7ies a!" 7o!trolli!g a7tio!s o' other immu!e 7ells.

3si!g a!imal mo"els, 6asatiempo et al >2?ha;e sho$! that !ormal a!ti&o"y 'u!7tio! isimpaire" i! early stages o' ;itami! "e'i7ie!7y. Bo$ma! et al >1?ha;e sho$! "e7reases

i! E 7ell a7ti;ity a!" i! i!ter'ero! (I?

301

Other Biologic Actions of Vitamin A

Vitami! has esse!tial roles i! &o!e "e;elopme!t, the "e;elopme!t a!" mai!te!a!7e o'

epithelial tissue, !ormal repro"u7tio!, a!" ;isio!. By ;irtue o' its e''e7t o! protei!

sy!thesis a!" &o!e 7ell "i''ere!tiatio!, it is !e7essary 'or gro$th a!" "e;elopme!t o's%eletal a!" so't tissues. Vitami! also plays a role i! mai!tai!i!g !ormal epithelial

stru7tures, i!7lu"i!g the "i''ere!tiatio! o' &asal 7ells i!to mu7ous epithelial 7ells. >52?

Vitamin A and Osteoarthritis

lthough there is great pote!tial 'or a role o' ;itami! i! 4, there is ;irtually !o

literature that has reporte" a prote7ti;e asso7iatio! o' "ietary or suppleme!tal reti!ol or&eta-7arote!e i! relatio! to the i!itiatio! or progressio! o' 4.
http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315012http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315012http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315012http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315002http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315002http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315002http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315077http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315077http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315077http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315009http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315009http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315009http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315010http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315010http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315010http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315009http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315009http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315009http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315062http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315062http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315062http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315016http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315016http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315016http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315077http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315077http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315077http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315077http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315077http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315077http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315067http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315067http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315067http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315052http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315052http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315052http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315012http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315002http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315077http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315009http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315010http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315009http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315062http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315016http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315077http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315077http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315067http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315052


8/22

VITAMIN C ASCOR@IC ACID-

Vitami! C, the a!tis7or&uti7 ;itami!, >52?is 7hemi7ally the least 7omple= o' the ;itami!s.lthough pla!ts a!" ma!y mammals are a&le to sy!thesiAe as7or&i7 a7i" 'rom glu7ose

a!" gala7tose, huma!s, mo!%eys, a!" gui!ea pigs "o !ot sy!thesiAe ;itami! C 'rom

i!tri!si7 sour7es. s7or&i7 a7i" is easily a&sor&e" 'rom the small i!testi!e i!to the &loo"&y a! a7ti;e me7ha!ism a!" pro&a&ly also &y "i''usio!. ;erage a&sorptio! is 9F 'or

i!ta%es &et$ee! 2 to 12 mg ho$e;er, at ;ery high i!ta%es, su7h as 12 g, $hi7h are

o'te! sel'-me"i7ate", a&sorptio! is G2F (29? ho$e;er, o!7e the as7or&ate

a!tio=i"ati;e 7apa7ity has &ee! e=pe!"e", the remai!i!g $ater-solu&le a!tio=i"a!ts,

urate, &iliru&i!, a!" the protei! thiols, 7a! trap o!ly part o' the aueous pero=yl ra"i7als.#he pero=yl ra"i7als that es7ape these remai!i!g a!tio=i"a!ts i! the aueous phase

"i''use i!to the plasma lipi"s, $here they i!itiate lipi" pero=i"atio!. 4ther a!tio=i"a!ts

are a&le to slo$ the rate at $hi7h lipi" pero=i"atio! o77urs, $hereas as7or&ate 7a!
http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315052http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315052http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315052http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#F031503http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315029http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315029http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315029http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315029http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315029http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315029http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315052http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#F031503http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315029http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315029


9/22

pre;e!t i!itiatio! o' "ete7ta&le lipi" pero=i"atio! &y aueous pero=yl ra"i7als. >29?29?a!" has &ee!

i"e!ti'ie" as a s7a;e!ger o' se;eral ra"i7als. >05?

s7or&ate rea7ts rapi"ly $ith &oth supero=i"e a!" pero=yl ra"i7als a!" e;e! more rapi"ly

$ith hy"ro=yl ra"i7als.>10?

>21?

It also s7a;e!ges si!glet o=yge!, re"u7es thiol ra"i7als, a!"7om&i!es rapi"ly $ith hypo7hlorous a7i" at sites o' i!'lammatio!. Vitami! C is also

&elie;e" to ha;e a role i! spari!g or re7y7li!g o' alpha-to7opherol (;itami! :) >5/?>0?a!"has &ee! sho$! to spare 7arote!oi"s >0?i! ;itro. It plays a ;ital role i! mai!tai!i!g the

&ala!7e &et$ee! o=i"ati;e pro"u7ts a!" the ;arious 7ellular a!tio=i"a!t "e'e!se

me7ha!isms. #he i!ter"epe!"e!7y o' su7h rea7tio!s i!;ol;es as7or&i7 a7i", ;itami! :,sele!ium, 7atalase, a!" glutathio!e. >19?It is %!o$! that as7or&ate 7a! s$it7h 'rom a!ti- to

pro-o=i"a!t a7ti;ity, "epe!"i!g o! its 7o!7e!tratio! a!" the prese!7e o' 'ree tra!sitio!

metal io!s >?>5?>59? ho$e;er, i! plasma, tra!sitio! metal io!s are tightly &ou!" a!"u!a;aila&le 'or 'ree ra"i7al rea7tio!s. >19?>05?>0?>0?

#he a!tio=i"a!t prote7tio! a''or"e" &y as7or&ate "oes !ot 7orrelate li!early $ith its7o!7e!tratio! i! the prese!7e o' u!restri7te" i!ta%e. With i!7reasi!g 7o!7e!tratio!s o'

as7or&ate, its e''i7ie!7y 'or s7a;e!gi!g 'ree ra"i7als "e7li!es. ata 'rom the $or% o' 29?suggest that a! i!7rease i! the + 'or as7or&ate 'rom the 7urre!t mg to

appro=imately 15 mg (to ma=imiAe the total &o"y pool o' as7or&ate) $oul" &e &e!e'i7ial

to huma! health.

Vitamin C and the Immune Response

0?ha;e "es7ri&e" plasma as7or&ate as &ei!g outsta!"i!gly e''e7ti;e agai!st the

o=i"a!ts release" 'rom a7ti;ate" polymorpho!u7lear leu%o7ytes. Vitami! C may promote

resista!7e to i!'e7tio! &y alteri!g the immu!ologi7 a7ti;ity o' leu%o7ytes, the pro"u7tio!o' i!ter'ero!, the i!'lammatory respo!se, or the i!tegrity o' the mu7ous mem&ra!es. >21?

s7or&ate has &ee! sho$! to ha;e a ma@or i!'lue!7e o! phago7yte mo&ility a!"

7hemota=is. >21?Be'ore parti7le i!gestio!, phago7ytes e=hi&it a mar%e" i!7rease i!

meta&oli7 a7ti;ity %!o$! as the respiratory &urst. 4=yge! 7o!sumptio! is greatly

i!7rease" a!" mu7h o' this e=tra o=yge!

303

is 7o!;erte" to rea7ti;e o=yge! meta&olites. #he +4 are release" i!to the phagosome to&e use" 'or %illi!g phago7ytose" mi7roorga!isms ho$e;er, +4 are also release" to the

e=terior o' the 7ell, $here they may "amage a"@a7e!t !ormal tissue. >?

ata 'rom gui!ea pigs ($hi7h, li%e huma!s, "o !ot sy!thesiAe ;itami! C) ha;e suggeste"

that ;itami! C i!ta%e is a 7riti7al 'a7tor i! the "e;elopme!t o' the immu!e respo!se. >?#hese mo"els 7o!'irm the role o' ;itami! C i! phago7yte 7ell 'u!7tio! a!" suggest

e''e7ts o! 7yto%i!e pro"u7tio!.
http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315029http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315029http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315029http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315029http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315029http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315029http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315035http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315035http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315035http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315013http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315013http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315013http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315021http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315021http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315021http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315058http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315058http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315058http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315073http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315073http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315073http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315073http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315073http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315073http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315019http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315019http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315019http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315007http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315007http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315007http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315050http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315050http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315050http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315059http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315059http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315059http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315019http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315019http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315019http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315035http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315035http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315035http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315036http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315036http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315036http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315037http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315037http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315037http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315029http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315029http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315029http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315030http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315030http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315030http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315021http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315021http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315021http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315021http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315021http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315021http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315076http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315076http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315076http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315076http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315076http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315076http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315029http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315029http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315035http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315013http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315021http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315058http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315073http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315073http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315019http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315007http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315050http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315059http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315019http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315035http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315036http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315037http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315029http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315030http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315021http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315021http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315076http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315076


10/22

u&7li!i7al as7or&ate "e'i7ie!7y 7a! &e relati;ely 7ommo!, e;e! i! a''lue!t so7ieties. >21?>2?

6hysiologi7 stress may 7ause a sharp "rop i! as7or&ate le;els, a!" may o77ur partly as a

result o' leu%o7yte migratio! to sites o' tissue i!@ury. >21?I!7reasi!g "osages o' ;itami! Ci! huma! ;olu!teers $ere 'ou!" to i!7rease !eutrophil 7hemota=is. >5?Vitami! C may a7t

at more that o!e le;el o' the immu!e respo!se, a!" at least some o' these i!tera7tio!s

i!;ol;e spe7i'i7 regulatio! o' the 7yto%i!e !et$or%.

Vitamin C and Osteoarthritis

Vitami! C a7ts as a! ele7tro! "o!or i! the sy!thesis o' type II 7ollage!, a primary

stru7tural 7ompo!e!t o' 7artilage. Vitami! C is i!;ol;e" i! the hy"ro=ylatio! o' proli!e

to 'orm hy"ro=yproli!e i! the sy!thesis o' 7ollage!. >0?It also plays a part i!gly7osami!ogly7a! sy!thesis through its role as a 7arrier o' sul'ate groups. >9?epletio!

o' sul'ate" proteogly7a!s 'rom the e=tra7ellular matri= o' arti7ular 7artilage is o!e o' the

earliest ma!i'estatio!s o' 4. #he higher le;els o' matri=-"egra"i!g e!Aymes that ha;e

&ee! sho$! to &e prese!t i! the "isease" tissue are thought to play a ma@or role i! this

loss.>9?

e'i7ie!7y o' ;itami! C, there'ore, 7oul" &e relate" to the re"u7e" me7ha!i7ali!tegrity o' the e=tra7ellular matri= o' arti7ular 7artilage a!" the i!7rease" matri=

tur!o;er rate i! 4. >10?>29?

7h$artA et al >?stu"ie" the "e;elopme!t o' surgi7ally i!"u7e" 4 i! gui!ea pigs that$ere gi;e! either high or lo$ (&ut !o!s7or&uti7) "ietary le;els o' ;itami! C. #hey

reporte" that gui!ea pigs mai!tai!e" o! high "ietary le;els o' ;itami! C "e;elope" less-

se;ere 4. #he 7artilage sur'a7es i! the surgi7ally mo"i'ie" @oi!ts sho$e" less loss o'7artilage, less pitti!g a!" ul7eratio!, a!" less e&ur!atio! i! the a!imals re7ei;i!g higher

"ietary le;els o' ;itami! C. I! !ormal arti7ular 7artilage, as7or&ate sig!i'i7a!tly i!7rease"

the &iosy!thesis o' sul'ate" proteogly7a!s a!" i!hi&ite" the a7ti;ity o' a7i" phosphatase.>1?

#hese properties o' ;itami! C presuma&ly 7o!tri&ute" to the i!7rease" 'ormatio! a!"sta&ility o' proteogly7a!s that su77ess'ully 7ou!tera7te" the erosio! o' 7artilage "uri!g

"e;elopme!t o' 4 i! this a!imal mo"el.

VITAMIN ! al+ha;TOCO%H!RO&-

ietary ;itami! : i!7lu"es the to7opherols--alpha, &eta, gamma, a!" "elta--a!" the

to7otrie!ols, $hose most importa!t 7hemi7al 7hara7teristi7 is their

30

a!tio=i"a!t property. &sorptio! o' ;itami! : is relati;ely i!e''i7ie!t, ra!gi!g &et$ee!

2F a!" /F. #his ;itami! is store" i! li;er a!", to a large e=te!t, i! 'atty tissues.

I! 'oo", ;itami! : a7ts to pre;e!t the pero=i"atio! o' 63


11/22

s7a;e!gi!g 'ree ra"i7als that 7o!tai! o=yge!, ;itami! : seems to prote7t 7ellular a!"

su&7ellular mem&ra!es 'rom "amage. I! the a&se!7e o' ;itami! :, 'ree ra"i7als 7atalyAe

pero=i"atio! o' the 632?#he e''e7ts o' ;itami! : a!" those o' sele!ium, sul'ur ami!o a7i"s,

polyu!saturate" 'atty a7i"s, a!" other a!tio=i"a!ts are i!ter"epe!"e!t. >5?

#i)ure .alpha-#o7opherol.

305

Vitami! : may &e &e!e'i7ial to the &o"yHs host "e'e!se me7ha!isms &y pre;e!ti!g the

i!'e7tio!-i!"u7e" i!7rease i! pro"u7tio! o' tissue prostagla!"i!s 'rom ara7hi"o!i7 a7i".
http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315018http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315018http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315018http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315060http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315060http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315060http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#F031504http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#F031504http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315018http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315018http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315018http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315027http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315027http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315027http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315057http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315057http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315057http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315018http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315060http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#F031504http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315018http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315027http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315057


12/22

>5?6rostagla!"i! pro"u7tio! reuires a! a7ti;e o=yge! spe7ies, a!" lipi" pero=i"es 7a!

stimulate sy!thesis &y pro;i"i!g a! o=yge! spe7ies.

8oetAl >02?reporte" that ;itami! : &i"ire7tio!ally mo"ulate" the a7ti;ity o' thelipo=yge!ase path$ay o' huma! !eutrophils i! ;itro a!" that !ormal plasma

7o!7e!tratio!s o' ;itami! : e!ha!7e" the lipo=yge!atio! o' ara7hi"o!i7 a7i", $hereashigher 7o!7e!tratio!s e=erte" a suppressi;e e''e7t, 7o!siste!t $ith the role o' alpha-

to7opherol as a hy"ropero=i"e s7a;e!ger. Whe! e!"othelial 7ells are e=pose" to o=i"ati;estress, they sy!thesiAe more 68I2, $hi7h may &e a prote7ti;e respo!se agai!st i!@ury. >15?

Mey"a!i et al >5?ha;e sho$! that ;itami! : suppleme!tatio! i! mi7e i!7reases lu!g 68I 2

sy!thesis.

Vitamin ! and the Immune Response

#he mou!ti!g o' a! immu!e respo!se reuires mem&ra!e-&ou!", re7eptor-me"iate"

7ommu!i7atio! &et$ee! 7ells a!" &et$ee! protei! a!" lipi" me"iators. #his 7a! &e

"ire7tly or i!"ire7tly a''e7te" &y to7opherol status, although the pre7ise me7ha!ism is !ot%!o$!. >5?6re;ious $or% has sho$! that 'ree ra"i7al a!" lipi" pero=i"atio! rea7tio!s play

a part i! 7ellular "amage. >9?

:;i"e!7e 'rom a!imal mo"els sho$s that ;itami! : is prote7ti;e agai!st e!;iro!me!tal

polluta!ts, "e7reases throm&osis, re"u7es the 'ormatio! o' 7ertai! 7ar7i!oge!s, a!"e!ha!7es almost e;ery aspe7t o' the immu!e respo!se. #he resista!7e to i!'e7tio!,

spe7i'i7 a!ti&o"y respo!ses, sple!i7 plaue-'ormi!g 7ells, i! ;itro mitoge!i7 respo!ses o'

lympho7ytes, reti7uloe!"othelial system 7leara!7e, a!" phago7ytosis all are altere" &y;itami! : "e'i7ie!7y. I!7reases i! to7opherol i!ta%e ha;e a positi;e impa7t o! these

pro7esses. >5?

tu"ies i! huma!s i!"i7ate that healthy i!"i;i"uals eati!g !ormal "iets sho$ a

sig!i'i7a!t "e7rease i! mar%ers o' 7ell "amage, su7h as lipi" pero=i"atio! a!" pe!ta!eoutput, $he! they suppleme!t their "iets $ith ;itami! :. >/?>5?#hese stu"ies suggest that

the a;erage "iet may !ot pro;i"e a"euate prote7tio! agai!st 'ree-ra"i7al "amage.

Vitamin ! and Osteoarthritis

#here ha;e &ee! 'e$ stu"ies o' ;itami! : a7ti;ity i! relatio! to 4. I! a 7ross-o;er stu"y,

29 4 patie!ts $ere ra!"omly assig!e" to treatme!t $ith to7opherol, mg a "ay 'or1 "ays, or to the pla7e&o group.

30

Ma7htey et al >51?'ou!" that 52F o' those re7ei;i!g ;itami! : e=perie!7e" mar%e" relie'o' pai!, as 7ompare" $ith o!ly 1 patie!t (F) i! the pla7e&o group.
http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315057http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315057http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315057http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315032http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315032http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315032http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315015http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315015http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315015http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315057http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315057http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315057http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315057http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315057http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315057http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315079http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315079http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315079http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315057http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315057http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315057http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315048http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315048http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315048http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315075http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315075http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315075http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315051http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315051http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315051http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315057http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315032http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315015http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315057http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315057http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315079http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315057http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315048http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315075http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315051


13/22

VITAMIN D

#he pre7ursors o' ;itami! are prese!t i! sterol 'ra7tio!s o' a!imal a!" pla!t tissues i!the 'orm o' -"ehy"ro7holesterol a!" ergosterol, respe7ti;ely. Both pre7ursors reuire

ultra;iolet irra"iatio! 'or 7o!;ersio! to the pro;itami! 'orm (0, 7hole7al7i'erol, a!" 2)

a!" &oth pro;itami!s reuire 7o!;ersio! i! the %i"!ey to the meta&oli7ally a7ti;e 'orm.#he pla!t 'orm is o' i!terest primarily as a 'oo" a""iti;e (52?

#he + 'or ;itami! is 1 mug ( I3) 'or 7hil"re! &eyo!" mo!ths o' age, you!g

a"ults up to 25 years o' age, a!" preg!a!t a!" la7tati!g $ome!. 52?

#i)ure 5.tru7tural 'ormulae a!" 7o!;ersio! o' pro;itami! to ;itami! .
http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#F031505http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315052http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315052http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315052http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315052http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315052http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315052http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#F031505http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315052http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315052


14/22

30=

Vitamin D and Osteoarthritis

+elati;ely little is %!o$! o' the "ire7t a7tio!s o' ;itami! a!" its meta&olites i! arthritis.

It is li%ely that ;itami! meta&olites are 7o!7er!e" $ith !ormal 7artilage i!tegrity, >25?&ut

spe7i'i7 meta&oli7 a7tio!s are !ot $ell "e'i!e".

It has &ee! sho$! that 7ulture" 7ho!"ro7ytes 7o!;ert ;itami! to its a7ti;e 'orms. >25?>01?25?'ou!" sig!i'i7a!t amou!ts o' 25-4*- a!" 2, 25-(4*)2- i! samples o'

sy!o;ial 'lui" 'rom patie!ts $ith 4 a!" rheumatoi" arthritis (+). erum le;els o' 25-

4*- $ere, o! a;erage, t$i7e as great as those i! sy!o;ial 'lui" 'rom the same patie!t.

#he i!;estigators suggeste" that the 7ompositio! o' sy!o;ial 'lui" is 7o!siste!t $ith it&ei!g a "ialysate o' plasma i!to $hi7h hyaluro!a! is se7rete" &y the sy!o;ial mem&ra!e.

#here'ore, the prese!7e o' ;itami! meta&olites i! sy!o;ial 'lui" may simply re'le7t the

serum ;alues. I! 7o!trast, a!alyses o' 2, 25-(4*)2- i! samples o' sy!o;ial 'lui" a!"serum suggeste" lo7al pro"u7tio! o' that meta&olite i! the sy!o;ium, rather tha! o!ly

"i''usio! i!to the @oi!t spa7e 'rom serum. o "i''ere!7es $ere !ote" &et$ee! results o'

assays o' sy!o;ial 'lui" 'rom patie!ts $ith 4 a!" those $ith +.

I!terest i! ;itami! i!7rease" $he!, i! 199, the


15/22

55?'ou!" !o prote7tio! 'or ;itami! $ith the "e;elopme!t o'

i!7i"e!t 4.

30>

#his stu"y, $hi7h has stimulate" mu7h i!terest 'rom pra7titio!ers a!" patie!ts, i! truth

merely highlights the !ee" to stu"y the role o' !utritio! $ith a 7lear se!se o' the

multi'a7torial !ature o' 4 a!" the multiple roles that a spe7i'i7 !utrie!t may ha;e i!7ellular physiology.

Vitamin D" the Immune Response" and Osteoarthritis

4!e possi&le e=pla!atio! 'or the role ;itami! may ha;e playe" i! the progressio! o'

4 amo!g the ?or &a7terial lipopolysa77hari"es. >5?*ayes et al >1?ha;e spe7ulate" that a7ti;ate"

ma7rophages i! patie!ts $ith arthritis sy!thesiAe 1, 25-(4*)2- $ithi! the a''e7te"

@oi!ts. #hese i!;estigators e=ami!e" sy!o;ial 'lui" samples 'rom 5 patie!ts $ith %!eee''usio!s a!" sho$e" that sy!o;ial 'lui" 7ells $ere 7apa&le o' sy!thesiAi!g the a7ti;e

;itami! meta&olite 1, 25-(4*)2- a!" that a7ti;ate" ma7rophages appeare" to &e

respo!si&le 'or mu7h o' the 1, 25(4*)2- sy!thesiAe". lthough the sig!i'i7a!7e o' thea&ility o' ma7rophages 'rom patie!ts $ith i!'lammatory arthritis to sy!thesiAe 1, 25-

(4*)2- is !ot 7lear, *ayes et al >1?spe7ulate that the importa!7e may &e greater $he!

the 7ells are prese!t $ithi! the sy!o;ial mem&ra!e, a!" thus a"@a7e!t to the sites o' tissue

"amage a!" &o!e erosio! $ithi! the @oi!t, tha! $he! they are prese!t i! the sy!o;ial'lui".

4;erall, spe7i'i7 re7eptors 'or 1, 25-(4*)2- o! !ormal huma! mo!o7ytes, a7ti;ate"

lympho7ytes, a!" peripheral &loo" lympho7ytes a!" sy!o;ial 'i&ro&lasts 'rom patie!ts$ith rheumatoi" arthritis >1?suggest a physiologi7 role 'or the meta&olite i! @oi!t "isease.

Ma!y o' the reporte" e''e7ts o' 1, 25-(4*)2- may &e rele;a!t to 4. 01?*ayes et al "i" !ot 'i!" e;i"e!7e o' sy!thesis o' 2, 25-(4*) 2

i! sy!o;ial 'lui" 7ells o' the 5 patie!ts $ith %!ee e''usio!s "es7ri&e" pre;iously. >1?

Vitamin D" Cell Differentiation" Bone" and Immunologic Responsiveness
http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315055http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315055http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315055http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315041http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315041http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315041http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315046http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315046http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315046http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315065http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315065http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315065http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315041http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315041http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315041http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315041http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315041http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315041http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315041http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315041http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315041http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315074http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315074http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315074http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315066http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315066http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315066http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315031http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315031http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315031http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315041http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315041http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315041http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315055http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315041http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315046http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315065http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315041http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315041http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315041http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315074http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315066http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315031http://www.mdconsult.com/das/article/body/97264410-4/jorg=journal&source=&sp=10752987&sid=0/N/145634/1.html?issn=0889-857X&printing=true#R0315041


16/22

Vitami! plays multiple roles that ultimately may ha;e a! e''e7t i! 4. #he hormo!al

'orm o' ;itami! (1, 25-(4*)2-) i!hi&its 7ollage!

304

sy!thesis &y osteo&lasts a!" promotes &o!e resorptio!. *ormo!al ;itami! there'ore

may 7o!tri&ute to 4 status i!so'ar as 4 is "etermi!e" &y &o!e mi!eral "e!sity. I!

a""itio!, 1, 25-(4*)2- promotes "i''ere!tiatio! o' mo!o7ytes i!to ma7rophages a!" the'usio! o' ma7rophages i!to multi!u7leate" gia!t 7ells. #hese gia!t 7ells 7a! ha;e multiple

'u!7tio!s, i!7lu"i!g a humoral immu!ologi7al respo!se a!" stimulatio! o' &o!e

resor&i!g a7ti;ity &y osteo7lasts. >1?1, 25-(4*)2- also a7ts upo! # lympho7ytes,pro"u7i!g a ;ariety o' lympho%i!es, i!7lu"i!g the pote!t &o!e resor&i!g age!t osteo7last

a7ti;ati!g 'a7tor. >?Withi! the sy!o;ial 'lui" a!" sy!o;ium 1, 25-(4*)2- thus may ha;e

7omple= para7ri!e a!" immu!oregulatory 'u!7tio!s. >1?It is also importa!t to !ote thatthese roles are playe" &y the hormo!al 'orm o' ;itami! , a 'orm that is o!ly i!"ire7tly

asso7iate" $ith measures o' "ietary ;itami! i!ta%e, su!light e=posure, a!" serum le;elso' 25-hy"ro=y;itami! .

SMMARB

#here are at least 'our me7ha!isms $here&y the !utrie!t ;itami!s , C, , a!" : may &erelate" to the pro7esses that impe"e or gi;e rise to 4. #hese !utrie!t ;itami!s ha;e

ma@or roles i! mo"ulati!g o=i"ati;e stress, parti7ipati!g i! immu!e respo!ses, a!"

7o!tri&uti!g to 7ell "i''ere!tiatio!. #here is a su&sta!tial !ee" to u!"ersta!" the

7o!tri&utio! o' these !utrie!ts to 4, &e7ause they may pro;i"e importa!t i!sight i!toameliorati!g the i!itiatio! a!" progressio! o' the "isease. imulta!eously, greater

u!"ersta!"i!g $ill a"" ratio!ality to a! area o' pote!tial i!ter;e!tio! that is o'te! &ase"

o! a!e7"ote.

I!;estigatio! $ill &e 7omple= there is the !ee" to sele7t appropriate systems. #ypi7ala!imal mo"el systems use" i! the stu"y o' 4 are i!appropriate &e7ause most a!imals

7a! sy!thesiAe as7or&i7 a7i". #here is the !ee" to "isaggregate, as mu7h as possi&le, the

!umerous su&sets o' 4 a!" the plethora o' pro7esses that 7o!tri&ute to thatheteroge!eity. Certai!ly, there is the !ee" to re7og!iAe the i!ter"epe!"e!7y o' the a7tio!s

o' ea7h o' these !utrie!ts at the 7ellular le;el.


17/22

1. &e :, Miyaura C, #a!a%a *, et al 1alpha,25-ihy"ro=y;itami! 0 promotes 'usio! o' mouse al;eolar

ma7rophages &oth &y "ire7t me7ha!ism a!" &y splee! 7ell-me"iate" i!"ire7t me7ha!isms. 6ro7 atl 7a"

7i 3 /550, 19/0 &stra7t

2. le=a!"er M, e$mar% *, Miller 8 4ral &eta-7arote!e 7a! i!7rease the !um&er o' 4E# positi;e 7ells

i! huma! &loo". Immu!ology 9221, 19/5

0.

33?

li K, :;a!s :!Aymati7 "egra"atio! o' 7artilage i! osteoarthritis.


18/22

7ell a7ti;ity a!" i!ter'ero! pro"u7tio! i! rats. L utr 1212, 199 &stra7t

1. Bur%har"t *, 7h$i!gel M, Me!!i!ger * 4=yge! ra"i7als as e''e7tors o' 7artilage "estru7tio!. rthritis

+heum 2909, 19/ &stra7t

1/. Burto! 8W Vitami! : !tio=i"a!t a7ti;ity, &io%i!eti7s, a!" &ioa;aila&ility. !! +e; utr 105,

199

19. Burto!-Wurster , Butler M, *arter , et al 6rese!7e o' 'i&ro!e7ti! i! arti7ular 7artilage i! t$o a!imal

mo"els o' osteoarthritis. L +heumatol 1015, 19/ &stra7t

2. Chrisma! 4, a"e!&auer-Bellis IM, 6a!@a&i M #he relatio!ship o' me7ha!i7al trauma a!" the early

&io7hemi7al rea7tio!s o' osteoarthriti7 7artilage. Cli! 4rthop 1125, 19/1

21. Cu!!i!gham-+u!"les W


19/22

01. 8ara&e"ia! M, ie&erherr M, H8uye! #M, et al #he i! ;itro pro"u7tio! a!" a7ti;ity o' 2,25-

"ihy"ro=y7hole7al7i'erol i! 7artilage a!" 7al;arium. Cli! 4rthop 10521, 19/

02. 8oetAl :L Vitami! : mo"ulates lipo=yge!atio! o' ara7hi"o!i7 a7i" i! leu%o7ytes. ature 2//1/0, 19/

&stra7t

00. 8ree!$al" + egra"atio! o' 7artilage proteogly7a!s a!" 7ollage! &y supero=i"e ra"i7al. rthritis

+heum 1999, 19

0. 8ree!$al" +, Mo= WW I!hi&itio! o' 7ollage! gelatio! &y a7tio! o' the supero=i"e ra"i7al. rthritis

+heum 22251, 199 &stra7t

05. *alli$ell B !tio=i"a!ts a!" huma! "isease ge!eral i!tro"u7tio!. utr +e; 55(uppl), 199Citatio!

0. *alli$ell B, ruoma 4I "amage &y o=yge!-"eri;e" spe7ies Its me7ha!ism a!" measureme!t i!

mammalia! systems.


20/22

8ero!tology 055, 19/

/. emoy!e M, Va! 8ossum , Euria! + Breath pe!ta!e a!alyses as a! i!"e= o' lipi" pero=i"atio!

'u!7tio!al test o' ;itami! : status. m L Cli! utr 2, 19/ &stra7t

9. oeser +


21/22

0. 6eter%o's%y B s7or&ate reuireme!t 'or hy"ro=ylatio! a!" se7retio! o' pro7ollage! +elatio!ship to

i!hi&itio! o' 7ollage! sy!thesis i! s7ur;y. m L Cli! utr 5(suppl)1105, 1991 &stra7t

. 6uig-6arella"a 6, 6la!as LM y!o;ial 'lui" "egra"atio! i!"u7e" &y 'ree ra"i7als. Bio7hem 6harma7ol

2505, 19/ Citatio!

5. +ei7hel *, Eoe''ler 6, Bishop L:, et al 25-*y"ro=y;itami! 0meta&olism &y lipopolysa77hari"e-

stimulate" !ormal huma! ma7rophages. L Cli! :!"o7ri!ol Meta& 1, 19/ &stra7t

. +ei7hel *, Eoe''ler *6, orma! W y!thesis i! ;itro o' 1,25 &y i!ter'ero!-gamma-stimulate" !ormal

huma! &o!e marro$ a!" al;eolar ma7rophages. L Biol Chem 221901, 19/ &stra7t

. +oss C+ Vitami! a!" prote7ti;e immu!ity. utritio! #o"ay 21/, 1992

/. 7hal%$i@% L, Va! er Berg WB, Va! e 6utte B, et al *y"roge! pero=i"e suppresses the

proteogly7a! sy!thesis o' i!ta7t arti7ular 7artilage. L +heumatol 1225, 19/5 &stra7t

9. 7h$artA :+, "amy :''e7ts o' as7or&i7 a7i" o! arysul'atase a7ti;ities a!" sul'ate" proteogly7a!

meta&olism i! 7ho!"ro7yte 7ultures. L Cli! I!;est 9, 19 &stra7t

. 7h$artA :+, e;eille C+, te;e!s LW, et al 6roteogly7a! stru7ture a!" meta&olism i! !ormal a!"

osteoarthriti7 7artilage o' gui!ea pigs. rthritis +heum 2152/, 19/1 &stra7t

1. 7h$artA :+, 4h W*, e;eille C+ :=perime!tally i!"u7e" osteoarthritis i! gui!ea pigs Meta&oli7

respo!ses i! arti7ular 7artilage to "e;elopi!g pathology. rthritis +heum 2105, 19/1 &stra7t

2. #e! tate utritio! ur;ey i! the 3!ite" tates 19/-19. 3 Ce!ter 'or isease Co!trol, 3

epartme!t o' *ealth, :"u7atio! a!" Wel'are 6u&li7atio! o. (*M) 2-/102, 192

0. #homas WB, *olt 68 Vitami! C a!" immu!ity ! assessme!t o' the e;i"e!7e. Cli! :=p Immu!ol

020, 19/ &stra7t

. #sou%as C, 6ro;;e"i!i M, Ma!olagas C 1,25-ihy"ro=y;itami! 0 !o;el immu!oregulatory

hormo!e. 7ie!7e 2210/, 19/ &stra7t

5. Va! 8ossum , e Cuyper L, 4oms *, et al ssessme!t o' lipi" pero=i"atio! i! huma!s &y &reath

pe!ta!e output measureme!t. 7ta 8astroe!terol Belg 5525, 1992 Citatio!

. Watso! ++, :ar!est , 6ra&hala +* +eti!oi"s, 7arote!oi"s, ma7rophage a7ti;atio!.InCu!!i!gham-

+u!"les (e") utrie!t Mo"ulatio! o' the Immu!e +espo!se. e$ Kor%, Mar7el e%%er, 1990, p 0

. Watso! ++, 6ra&hala +*, 6leAia 6M, et al :''e7ts o' &eta-7arote!e o! lympho7yte su&populatio! i!

el"erly huma!s :;i"e!7e 'or a "ose respo!se relatio!ship. m L Cli! utr 509, 1991 &stra7t

/. Watso! ++, +y&s%i L Immu!omo"ulatio! &y reti!oi"s a!" 7arote!oi"s.InCha!"ra +E (e") utritio!

a!" Immu!ology. e$ Kor%, Wiley-iss, 19//, p /
http://www.mdconsult.com/das/journal/view/N/1908734?PAGE=1.html&source=MI&ANCHOR=abshttp://www.mdconsult.com/das/journal/view/N/1908734?PAGE=1.html&source=MI&ANCHOR=abshttp://www.mdconsult.com/das/journal/view/N/5239571?PAGE=1.html&source=MIhttp://www.mdconsult.com/das/journal/view/N/7705226?PAGE=1.html&source=MI&ANCHOR=abshttp://www.mdconsult.com/das/journal/view/N/7705226?PAGE=1.html&source=MI&ANCHOR=abshttp://www.mdconsult.com/das/journal/view/N/8783856?PAGE=1.html&source=MI&ANCHOR=abshttp://www.mdconsult.com/das/journal/view/N/7586735?PAGE=1.html&source=MI&ANCHOR=abshttp://www.mdconsult.com/das/journal/view/N/7586735?PAGE=1.html&source=MI&ANCHOR=abshttp://www.mdconsult.com/das/journal/view/N/5864584?PAGE=1.html&source=MI&ANCHOR=abshttp://www.mdconsult.com/das/journal/view/N/6215889?PAGE=1.html&source=MI&ANCHOR=abshttp://www.mdconsult.com/das/journal/view/N/6207084?PAGE=1.html&source=MI&ANCHOR=abshttp://www.mdconsult.com/das/journal/view/N/5644198?PAGE=1.html&source=MI&ANCHOR=abshttp://www.mdconsult.com/das/journal/view/N/7050529?PAGE=1.html&source=MI&ANCHOR=abshttp://www.mdconsult.com/das/journal/view/N/2021918?PAGE=1.html&source=MIhttp://www.mdconsult.com/das/journal/view/N/2288733?PAGE=1.html&source=MI&ANCHOR=abshttp://www.mdconsult.com/das/journal/view/N/1908734?PAGE=1.html&source=MI&ANCHOR=abshttp://www.mdconsult.com/das/journal/view/N/5239571?PAGE=1.html&source=MIhttp://www.mdconsult.com/das/journal/view/N/7705226?PAGE=1.html&source=MI&ANCHOR=abshttp://www.mdconsult.com/das/journal/view/N/8783856?PAGE=1.html&source=MI&ANCHOR=abshttp://www.mdconsult.com/das/journal/view/N/7586735?PAGE=1.html&source=MI&ANCHOR=abshttp://www.mdconsult.com/das/journal/view/N/5864584?PAGE=1.html&source=MI&ANCHOR=abshttp://www.mdconsult.com/das/journal/view/N/6215889?PAGE=1.html&source=MI&ANCHOR=abshttp://www.mdconsult.com/das/journal/view/N/6207084?PAGE=1.html&source=MI&ANCHOR=abshttp://www.mdconsult.com/das/journal/view/N/5644198?PAGE=1.html&source=MI&ANCHOR=abshttp://www.mdconsult.com/das/journal/view/N/7050529?PAGE=1.html&source=MI&ANCHOR=abshttp://www.mdconsult.com/das/journal/view/N/2021918?PAGE=1.html&source=MIhttp://www.mdconsult.com/das/journal/view/N/2288733?PAGE=1.html&source=MI&ANCHOR=abs


22/22

9. Koshi%a$a #, #a!a%a *, Eo!"o M :''e7t o' ;itami! : o! a"@u;a!t arthritis i! rats. Bio7hemi7al

Me"i7i!e 2922, 19/0

:mail to Colleague6ri!t Versio!

Copyright 2/ :lse;ier I!7. ll rights reser;e". - $$$.m"7o!sult.7om

@oo6mar6 R&

Vitamins and Arthritis the Roles of Vitamins A

Documents