http://www.wha-www.org/en/library/library.php?

studies=cardiovasculardisease
Cardiovascular Disease
The following pages provide an overview of the most recent research and clinical studies
about the health benefits of micronutrients in fighting cardiovascular disease. This collection
of scientific facts proves that anyone who privately or publicly questions the health value of
micronutrients does not serve Y!" health# or the health of the people# but rather the multi-
billion dollar investment $business with disease$ based on patented pharmaceutical drugs.
%e encourage you to forward the lin& to this important online library on natural health ' one
of the largest ones in the world ' to your friends. You may also print out the articles you find
most important for your own health condition and share them with your doctor. (ny
responsibly acting health professional will be grateful to receive such science-based health
education.
A 3-year study shows that vitamin C consumption slows progression in thickening of
coronary artery in elderly men.
)ncrease inta&es of vitamin * and antio+idant rich fruits and vegetables in the diet of ,--
elderly men over - years slowed the thic&ening of their carotid arteries as compared to ,-.
elderly men who did not increase their inta&e of antio+idant rich foods.
Vitamin C consumption is associated with less progression in carotid intima media thickness in elderly
men: A 3-year intervention study.
/ource: 0utr 1etab *ardiovasc 2is. ,334 5an6.47.8:9-.:.
(uthor: ;llingsen )# /el<eflot )# (rnesen =# Tonstad /.
(ffiliation: 2epartment of >reventive *ardiology# !llev?l !niversity =ospital# slo# 0orway.
ingrid.ellingsen@uus.no
(bstract: A(*BC"!02 (02 ()1: >lant foods may lower the ris& of cardiovascular
disease. 1;T=2/ (02 ";/!DT/: %e assessed changes in the intima media thic&ness
7)1T8 of the carotid artery and diet in elderly men. 1en 7n=EF-8 aged G3H/-E years were
randomly assigned to . of : groups 7dietary intervention# omega-- supplementation# both or
neither8 using a , + , factorial design. A-mode ultrasound of the carotid arteries and
calculation of dietary inta&e were performed at baseline and after - years. %e previously
showed that omega-- supplementation did not influence the )1T# thus the dietary intervention
7n=,--8 and no dietary intervention 7n=,-.8 groups were pooled. The dietary intervention
group had less progression in the carotid )1T compared with the controls 73.3::H/-3.34. mm
versus 3.3F,H/-3..3E mm6 >=3.3:G8. This group increased their daily vitamin * inta&e
7>=3.33E8 and inta&e of fruit# berries and vegetables 7>Ior=3.33.8. )ncreased inta&e of
vitamin * and of fruit and berries was inversely associated with )1T progression 7r=-3..9.6
>=3.33F and r=-3..,E6 >=3.3EF# respectively8. 1ultivariate linear regression analysis showed
that increased inta&es of vitamin * and of fruit and berries were associated with less )1T
progression in the intervention group and in the total study population# after ad<ustment for
consumption of dietary cholesterol# cheese# saturated fat and group assignment.
*0*D!/)0: Jitamin * containing foods may protect against the progression of carotid
atherosclerosis in elderly men.
http://www.ncbi.nlm.nih.gov/pubmed/.9:G,:34
A complex of antioxidant vitamins effectively inhiits free-radical oxidation of
phospholipids in lood plasma! liver and myocardium.
This study suggests that supplements containing antio+idant vitamins 7 Jitamin *# ;#
provitamin (8 and selenium can be effective for prevention and comple+ therapy of
atherosclerosis.
A complex of antioxidant vitamins effectively inhiits free-radical oxidation of "D" phospholipids in
lood plasma and memrane structures of the liver and myocardium.
/ource: Aull ;+p Aiol 1ed. ,33- Keb6.-E7,8:.:--F.
(uthor: Bonovalova CC# Disina 1# Ti&haLe (B# Dan&in JM.
(ffiliation: Daboratory of Aiochemistry of Kree-"adical >rocesses# (. D. 1yasni&ov )nstitute
of *ardiology# "ussian *ardiology "esearch-and->roduction *enter# "ussian 1inistry of
=ealth# 1oscow.
(bstract: (ntio+idant effect of a comple+ preparation including antio+idant vitamins *# ;#
provitamin ( and selenium was studied on the model of *u7,H8-initiated free-radical
o+idation of D2D isolated from human blood plasma. The antio+idant effect of combined
administration of alpha-tocopherolHascorbic acid and alpha-tocopherolHbeta-carotene is far
more pronounced that the antio+idant effect of individual components of these coc&tails.
1oreover# in the model system the combined action of all antio+idant components completely
inhibited free-radical o+idation of D2D. ( -3-day course of peroral administration of
antio+idant vitamin coc&tail and selenium to rats pronouncedly enhanced the antio+idant
potential of liver and completely suppressed free-radical processes in the myocardium. )t is
suggested that preparations containing antio+idant vitamins and selenium can be perspective
for prevention and comple+ therapy of atherosclerosis.
http://www.ncbi.nlm.nih.gov/pubmed/.,93,:.4
A component of hot peppers! Capsaicin! protects against lipid oxidation and protein
damage in human red lood cells.
*apsaicin# responsible for the heat or spice properties of hot peppers can protect blood cells
from the negative effects of o+idiLed fats and protein damage associated with too high
glucose blood levels . This is <ust one e+ample of the plethora of molecules found in common
herbs that have powerful medicinal properties in respect to cardiovascular health that wor&
with the same principles sought after by pharmaceutical industries.
#rotection of lipid peroxidation and caronyl formation in proteins y capsaicin in human erythrocytes
su$ected to oxidative stress.
/ource: >hytother "es. ,33F (pr6,37:8:-3--F.
(uthor: Duqman /# "iLvi /).
(ffiliation: 2epartment of Aiochemistry# !niversity of (llahabad# (llahabad ,..33,# )ndia.
(bstract: *apsaicin 79-methyl-0-vanillyl-F-nonemide8 is the ma<or pungent principle found in
hot peppers of the plant genus *apsicum. The present wor& was underta&en to investigate the
antio+idative property of capsaicin on mar&ers of o+idative stress6 membrane lipid
pero+idation 7formation of malondialdehyde8 and membrane carbonyl groups in human
erythrocytes. The effect of capsaicin has been compared with l-ascorbic acid. /ub<ecting
erythrocytes to o+idative stress by incubating them with t-A=> caused a significant increase
in 12( level and protein carbonyl group content above the basal value. The presence of
capsaicin 7.3 microm8 in the incubation medium protected the erythrocytes from t-A=>-
induced o+idative stress as evidenced by the decrease in 12( level and protein carbonyl
group content# l-ascorbic acid also showed similar protective effect. The results conclusively
prove the efficacy of the antio+idant property of capsaicin. This evidence suggests that dietary
factors that act as antio+idants to decrease membrane lipid pero+idation and protein carbonyl
formation may contribute to a protective effect against cancer# atherosclerosis and age related
diseases. This antio+idant effect may# in part# e+plain the high consumption of capsicum in
certain regions of the world.
http://www.ncbi.nlm.nih.gov/pubmed/.FEEGF.:
Anti-inflammatory effects of Vitamin C
)n people with elevated levels of *-reactive protein 7*">8 which indicates inflammation# an
inta&e of . gram of vitamin * and 933 )! vitamin ; for , months reduced this mar&er as
effectively as statins. *ontrary to statins these nutrients do not trigger unwanted side effects.
)n addition# vitamin * supplementation did not lower *"> in those with normal *"> levels#
suggesting that micronutrients alleviate pathology but do not disturb metabolic balance in
healthy conditions.
Vitamin C treatment reduces elevated C-reactive protein.
/ource: Kree "adic Aiol 1ed. ,334 5an .6:F7.8:G3-G.
(uthor: Aloc& C# 5ensen *2# 2alvi TA# 0or&us ;># =udes 1# *rawford >A# =olland 0#
Kung ;A# /chumacher D# =armatL >.
(ffiliation: !niversity of *alifornia# Aer&eley# 4:G,3# !/(. gbloc&@ber&eley.edu
(bstract: >lasma *-reactive protein 7*">8 is an inflammatory biomar&er that predicts
cardiovascular disease. Dowering elevated *"> with statins has reduced the incidence of
cardiovascular disease. %e investigated whether vitamin * or ; could reduce *">. =ealthy
nonsmo&ers 70=-4F8 were randomiLed to three groups# .333 mg/day vitamin *# 933 )!/day
vitamin ;# or placebo# for , months. 1edian baseline *"> was low# 3.9E mg/D. 0o treatment
effect was seen when all participants were included. =owever# a significant interaction was
found# indicating that treatment effect depends on baseline *"> concentration. (mong
participants with *"> indicative of elevated cardiovascular ris& 7N or =..3 mg/D8# vitamin *
reduced the median *"> by ,E.-O vs placebo 7p=3.3,8 7median reduction in the vitamin *
group# 3.,E mg/D# .F.GO8. These effects are similar to those of statins. The vitamin ; effect
was not significant. )n summary# treatment with vitamin * but not vitamin ; significantly
reduced *"> among individuals with *"> N or =..3 mg/D. (mong the obese# GEO had *">
N or =..3 mg/D. "esearch is needed to determine whether reducing this inflammatory
biomar&er with vitamin * could reduce diseases associated with obesity. Aut research on
clinical benefits of antio+idants should limit participants to persons with elevations in the
target biomar&ers.
http://www.ncbi.nlm.nih.gov/pubmed/.94E,.F:
Antioxidant sustances can prevent adhesion of white lood cells to inflamed endothelial
vascular wall cells.
%hite blood cells attach to receptors e+posed by inflamed cells of the artery lining. This
accellerates formation of atherosclerotic lesion. This in vitro study identified compounds that
can prevent this process. These compounds include vitamin *# ;# and resveratrol.
%on-radioactive and colorimetric &uantification of monocyte adhesion to endothelial cells in early
atherogenesis.
/ource: Aiotechnol Dett. ,33F 0ov6,97,,8:.93E-.3.
(uthor: 5un =5# *hung 15# Bim /Y# Dee =5# Dee /5.
(ffiliation: 2ivision of Kood /cience# *ollege of Dife /cience and Aiotechnology# )nstitute of
Aiomedical /ciences and /afety# Borea !niversity# /eoul# .-F-G.-# Borea.
(bstract: 1onocyte adhesion to vascular endothelium is an initial step in atherogenesis. To
quantify this# we incubated monocytes with cultured endothelial cells# and quantified the
adhered live monocytes using a colorimetric assay. ;ndothelium activated with
lipopolysaccharide attracted monocytes in a dose-dependent manner and the adhesion was
attenuated with post-treatments with D-ascorbic acid 7E-O8# alpha- 7:3O8 and gamma-
tocopherol 7-4O8# resveratrol 7-4O8# and Dithospermum erythrorhiLon root e+tract 7:EO8.
This non-radioactive# colorimetric assay may be useful for screening anti-atherogenic
compounds in early atherogenesis.
http://www.ncbi.nlm.nih.gov/pubmed/.G3,94.G
http://www.springerlin&.com/content/E-E:9F.FrGuE3.49/
Arterial 'mooth (uscle Cells #roduce Collagen in )esponse to %ormal "evels of
Ascoric Acid.
2r "athPs scurvy-heart disease connection emphasiLes the role of collagen for healthy
structure and function of the vascular wall and its resistance to cholesterol accumulation and
atherosclerotic plaque formation. . (rterial smooth muscle cells synthesiLe and attach
themselves to a networ& of collagen# elastin# proteoglycans# and adhesive molecules that give
arteries their unique properties of distending without tearing apart under high pressure# recoil
bac& to its original shape# and the ability to change diameter in response to e+ternal chemical
or nervous stimuli. %ithout collagen integrity# arteries are fragile and tear apart from blood
pressure as in the ;hlers-2anlos /yndrome. n the other hand# stiff arteries with too much
collagen are the result of metabolic compensation for abnormal conditions that impair artery
functions. %hile basic# the fact that the artery requires vitamin * 7ascorbic acid8 for
producing its internal collagen is still often ignored.
Ascoric acid uptake and regulation of type * collagen synthesis in cultured vascular smooth muscle cells.
/ource: 5 Jasc "es. ,3346:F7.8:.E-,:.
(uthor: Qiao =# Aell 5# 5uliao /# Di D# 1ay 51.
(ffiliation: 2epartment of 1edicine# Janderbilt !niversity /chool of 1edicine# 0ashville#
Tennessee -G,-,# !/(.
(bstract: A(*BC"!02/()1/: Jascular smooth muscle cells contribute both to the
structure and function of arteries# but are also involved in pathologic changes that accompany
inflammatory diseases such as atherosclerosis. /ince inflammation is associated with o+idant
stress# we e+amined the upta&e and cellular effects of the antio+idant vitamin ascorbic acid in
cultured (.3 vascular smooth muscle cells. 1;T=2//";/!DT/: (.3 cells concentrated
ascorbate against a gradient in a sodium-dependent manner# most li&ely on the sodium-
dependent vitamin * transporter type , 7/J*T,8 ascorbate transporter# which was present in
immunoblots of cell e+tracts. (lthough ascorbate did not affect (.3 cell proliferation# it
stimulated radiolabeled proline incorporation and type ) collagen synthesis. The latter was
evident in the cells as increases in proalpha.7)8 collagen and conversion of proalpha.7)8 and
proalpha,7)8 collagen to mature forms that were released from the cells and deposited as
e+tracellular matri+. )ntracellular type ) procollagen maturation was optimal at intracellular
ascorbate concentrations of ,33 micro1 and below# which were readily achieved by culture
of the cells at plasma physiologic ascorbate concentrations. *0*D!/)0: These results
show that the /J*T, facilitates ascorbate upta&e by vascular smooth muscle cells# which in
turn increases both the synthesis and maturation of type ) collagen.
http://www.ncbi.nlm.nih.gov/pubmed/.9E.E4G.
http://content.&arger.com/produ&tedb/produ&te.asp?typ=fullte+tRfile=333.-EFF.
Acidul ascoric restaileste functia arteriala la pacientii cu sindrom metaolic
1odificarile metabolice asociate diabetului afecteaLa negativ sistemul cardio-vascular.
(rterele persoanelor afectate de sindromul metabolic nu se deschid corespunLator
flu+ului sanguin. /tudiul de fata# realiLat in dublu-orb# arata ca administrarea intra
venoasa a . g de acid ascorbic duce la restabilirea functiei arteriale la pacientii cu
sindrom metabolic.
Disfunctia arteriala datorata stresului oxidativ la pacientii cu sindrom metaolic: +fectul acidului
ascoric
/ursa: Kree "adic Aiol 1ed. ,33G /ep .6:-7E8:9E--4.
(utori: *angemi "# (ngelico K# Doffredo D# 2el Aen 1# >ignatelli ># 1artini (# Jioli K.
(filiere: 2epartment of ;+perimental 1edicine and >athology# !niversity of "ome Da
/apienLa# "ome 33.F.# )taly.
"eLumat: 2isfunctia arteriala repreLinta un semn timpuriu de arteroscleroLa6 oricum# evolutia
acesteia la pacientii cu sindrom metabolic 7/18 este inca neclara. (m investigat rolul
stresului o+idativ prin dilatare mediata prin flu+ indus in conditii de ischemie 721K8 la
pacienti /1. 21K si stresul o+idativ# evaluat prin nivelul seric al 9-hidro+i-,-deo+i-,-
deo+iguanoLin 79-=dC8# au fost studiate la .9 subiecti cu /1 7lot studiu8 si -3 subiecti
sanatosi 7lot martor8. !lterior# la cei .9 pacienti cu /1# 21K a fost evaluata dupa
administraraea iv a .g de vitamina * sau de substanta placebo# intr-un studiu de tip caL
-control# dublu-orb# aleator6 probele de sange au fost recoltate inainte si dupa 21K# pentru a
masura 9-=dC. *omparativ cu lotul martor# pacientii cu /1 au preLentat nivel mai ridicat al
9-=dC 7pI3.33.8 si mai scaLut al 21K 7pI3.33.86 9-=dC si K12 au preLentat o corelatie
inversa 7"=-3.G:6pI3.3.8. Da pacientii cu /1 administrarea substantei placebo nu a modificat
21K 7pI3.33.8. 2upa administrarea substantei placebo# 21K in conditii de ischemie a fost
asociata cu valori semnificativ crescute ale 9-=dC 7pI3.33.8# un efect ce a fost contracarat
de catre vitamina *. )n<ectarea de vitamina * a fost asociata cu o inversa corelatie intre
modificarea K12 si stresul o+idativ 7"=-3.FG6pI3.3.8. (cest studiu releva faptul ca dilatarea
arteriala este insuficienta si ca accentuarea stresului o+idativ poate <uca un rol important la
pacientii cu /1.
http://www.ncbi.nlm.nih.gov/pubmed/.GFF:.:4
Aterosclero,a indusa prin dieta hiper-colesterolemianta la iepuri poate fi atenuata prin
suplimentare cu citrulina! arginina si vitaminele C si +
/uplimentarea cu aminoaciLi a dietelor hipercolesterolemiante la iepuri inverseaLa dramatic
procesul de ateroscleroLa.
'uplimentarea cu --citrulina si --arginina inversea,a procesul de aterosclero,a in ca,ul iepurilor cu dieta
hiper-colesterolemianta
/ursa: >roc 0atl (cad /ci ! / (. ,33E /ep ,36.3,7-98:.-F9.-F.
(utori: =ayashi T# 5uliet >(# 1atsui-=irai =# 1iyaLa&i (# Ku&atsu (# Kunami 5# )guchi (#
)gnarro D5.
(filiere: 2epartment of Ceriatrics# 0agoya !niversity Craduate /chool of 1edicine# FE
Tsuruma-cho# /howa-&u# 0agoya :FF-9EE3# 5apan. hayashi@med.nagoya-u.ac.<p
"eLumat: biectivul acestui studiu a fost de a evalua influenta ingestiei de .-arginina# .-
citrulina si antio+idanti 7vitaminele * si ;8 in progresul procesului aterosclerotic la iepuri
supusi unei diete hiper-colesterolemiante. 2ieta hiperlipidica a cauLat o insuficienta marcanta
a rela+arii vasculare la nivelul endotelial al aortei toracice iLolate# precum si a flu+ului
sanguin din artera auriculara la iepuri in vivo6 aparitia leLiunilor ateromatoase si cresterea
productiei de anioni supero+id la nivelul aortei toracice6 cresterea e+primarii genei
responsabile de sensibilitatea o+idativa 7raspunsul ;l&-. si (1> fosforilat in legarea
proteinelor8. )epurii au fost tratati pe cale orala timp de ., saptamani cu .-arginina plus .-
citrulina si/sau antio+idanti. .-arginina si .-citrulina# atat singure cat si in combinatie cu
antio+idanti produc o imbunatatire importanta a rela+arii vasculare la nivelul endotelial si a
flu+ului sanguin# o regresie importanta a leLiunilor ateromatoase si o scadere a productiei de
supero+id si a e+presiei genei responsabile de sensibilitatea o+idativa. (ceste efecte
terapeutice au fost asociate cu cresterea concomitenta in endoteliul aortic a e+primarii 0
sintetaLei si a nivelelor de 07,87-8H07-87-8 si cC1> plasmatice. (ceste observatii releva
faptul ca ingestia de substante stimulante de 0# inclusiv .-arginina# .-citrulina si
antio+idantii poate duce la indepartarea stresului o+idativ si la reversibilitatea procesului de
progresie a ateroscleroLei. (ceasta abordare poate avea o utilitate clinica in tratamentul
ateroscleroLei la om.
http://www.ncbi.nlm.nih.gov/pubmed/.F.EG99-
http://www.pnas.org/content/.3,/-9/.-F9..long
)olul enefic al vitaminei C in metaolismul celulei endoteliale
0ecroLa tumorala alfa 7T0K-a8 are un efect distructiv asupra celulelor mucoasei arteriale# a
caror leLare determina aparitia proceselor inflamatorii si a formarii de cheaguri.
Jitamina * 7acidul ascorbic8 este capabila de a contracara efectul distructiv al T0K-a
la nivelul endoteliului.
Acidul ascoric lochea,a cresterea efectului inhiitor a factorului de necro,a tumorala alfa la nivelul
celulelor endoteliale
/ursa: ;+p Aiol 1ed 71aywood8. ,33- 5ul6,,97G8:9EE-FE.
(utori: /aeed "%# >eng T# 1etL *0.
(filiere: Daboratory of Jascular Aiology# 2ivision of 1edicinal Aiochemistry# 0orth /hore-
Dong )sland 5ewish "esearch )nstitute# 1anhasset# 0ew Yor& ..3-3# !/(.
"eLumat: >roliferarea celulelor endoteliale depreciate a fost considerata un defect timpuriu si
critic ce contribuie la aparitia ateroscleroLei. /tudiile recente au demonstrat ca
nivelele plasmatice ridicate ale factorului necroLei tumorale 7T0K-a8 si nivelele
serice scaLute de acid ascorbic 7((8 sunt corelate cu gradul de severitate a
ateroscleroLei. )n plus# s-a constatat ca (( are un efect benefic in prevenirea
ateroscleroLei. AaLandu-ne pe aceste studii# am investigat rolul (( 7Isau=.m18
asupra inhibarii cresterii celulelor endoteliale vasculare mediata de T0K-a in vitro. )n
concordanta cu studiile anterioare# am constatat ca T0K-a singur inhiba proliferarea
celulelor endoteliale. /tudiile urmatoare au relevat ca (( singur accentueaLa
proliferarea celulelor endoteliale si ca (( blocheaLa inhibarea cresterii celulare
endoteliale indusa de T0K-a. 2in contra# nu am observat un efect al (( in activarea
celulelor endoteliale sau intrarea nucleara a factorului &appaA# ca raspuns la T0K-a.
;fectul protectiv al (( in proliferarea celulelor endoteliale nu a fost numai reLultatul
activitatii antio+idante a acestuia# ci a fost corelat cu sinteLa de colagen )J la nivelul
celulei endoteliale. >re-tratamentul cu (( a celulelor endoteliale proliferative a dus
la promovarea fosforilarii retinoblastomului 7"b8 si scaderea nivelului de pE-#
comparativ cu celulele netratate. 1ai mult de atat# suplimentarea de ((
cell proliferation was not simply the result of its antio+idant activity but did correlate with
collagen )J e+pression by endothelial cells. (( pre-treatment of proliferating endothelial
cells promoted retinoblastoma protein 7"b8 phosphorylation and decreased pE- levels when
compared to untreated cells. Kurthermore# the addition of (( to T0K-alpha-treated
proliferating endothelial cells bloc&ed both the inhibition of retinoblastoma protein
phosphorylation and enhanced pE- e+pression induced by T0K-alpha. *onsistent with these
results# we found that (( protects endothelial cells against T0K-alpha-induced apoptosis.
These studies highlight the potential therapeutic role of (( in promoting endothelial cell
proliferation during inflammatory conditions# such as atherosclerosis and cardiovascular
disease.
Ascoric acid restores arterial function in patients with (etaolic 'yndrome.
1etabolic changes associated with diabetes negatively affect the cardiovascular system.
(rteries of those with metabolic syndrome do not open normally in response to blood flow.
This placebo-controlled# randomiLed# double-blind study shows that intravenous
administration of . gram of ascorbic acid# allows to restore the function of arteries in patients
with metabolic syndrome.
.xidative stress-mediated arterial dysfunction in patients with metaolic syndrome: +ffect of ascoric
acid.
/ource: Kree "adic Aiol 1ed. ,33G /ep .6:-7E8:9E--4.
(uthor: *angemi "# (ngelico K# Doffredo D# 2el Aen 1# >ignatelli ># 1artini (# Jioli K.
(ffiliation: 2epartment of ;+perimental 1edicine and >athology# !niversity of "ome Da
/apienLa# "ome 33.F.# )taly.
(bstract: (rterial dysfunction is a hallmar& of early atherosclerosis6 however# its behavior in
patients with metabolic syndrome 71/8 is still unclear. %e investigated the role of o+idative
stress on ischemia-induced flow-mediated dilatation 7K128 in patients with 1/. K12 and
o+idative stress# as assessed by serum levels of 9-hydro+y-,-deo+y-,-deo+yguanosine 79-
=dC8# were studied in .9 1/ and -3 control sub<ects. Thereafter# in the .9 1/ patients#
K12 was assessed after iv infusion of . g vitamin * or placebo in a randomiLed# double-
blind# crossover design6 serial blood samples were ta&en in peripheral circulation before and
after K12 to analyLe 9-=dC. *ompared to controls# 1/ patients had higher 9-=dC
7pI3.33.8 and lower K12 7pI3.33.86 9-=dC and K12 were inversely correlated 7"=-3.G:6
pI3.3.8. )n 1/ patients# placebo administration did not change K12# whereas vitamin *
significantly enhanced it 7pI3.33.8. (fter placebo# ischemia-induced K12 was associated
with a significant increase in 9-=dC 7pI3.33.8# an effect that was counteracted by vitamin
*. Jitamin * infusion was associated with an inverse correlation between the changes in
K12 and o+idative stress 7"=-3.FG6 pI3.3.8. The present study shows that arterial dilatation
is impaired and that enhanced o+idative stress may play a &ey role in patients with 1/.
http://www.ncbi.nlm.nih.gov/pubmed/.GFF:.:4
Atherosclerosis induced y high-cholesterol-diet in raits can e attenuated y
supplementation with Citrulline! Arginine and Vitamin C and +
(mino acids supplementation in rabbits fed high cholesterol diets dramatically reverses
atherosclerosis.
l-Citrulline and l-arginine supplementation retards the progression of high-cholesterol-diet-induced
atherosclerosis in raits.
/ource: >roc 0atl (cad /ci ! / (. ,33E /ep ,36.3,7-98:.-F9.-F.
(uthor: =ayashi T# 5uliet >(# 1atsui-=irai =# 1iyaLa&i (# Ku&atsu (# Kunami 5# )guchi (#
)gnarro D5.
(ffiliation: 2epartment of Ceriatrics# 0agoya !niversity Craduate /chool of 1edicine# FE
Tsuruma-cho# /howa-&u# 0agoya :FF-9EE3# 5apan. hayashi@med.nagoya-u.ac.<p
(bstract: The ob<ective of this study was to evaluate the influence of ingested l-arginine# l-
citrulline# and antio+idants 7vitamins * and ;8 on the progression of atherosclerosis in rabbits
fed a high-cholesterol diet. The fatty diet caused a mar&ed impairment of endothelium-
dependent vasorela+ation in isolated thoracic aorta and blood flow in rabbit ear artery in vivo#
the development of atheromatous lesions and increased supero+ide anion production in
thoracic aorta# and increased o+idation-sensitive gene e+pression S;l&-. and phosphorylated
c(1> response element-binding proteinT. "abbits were treated orally for ., wee&s with l-
arginine# l-citrulline# and/or antio+idants. l-arginine plus l-citrulline# either alone or in
combination with antio+idants# caused a mar&ed improvement in endothelium-dependent
vasorela+ation and blood flow# dramatic regression in atheromatous lesions# and decrease in
supero+ide production and o+idation-sensitive gene e+pression. These therapeutic effects
were associated with concomitant increases in aortic endothelial 0 synthase e+pression and
plasma 07,87-8H07-87-8 and cC1> levels. These observations indicate that ingestion of
certain 0-boosting substances# including l-arginine# l-citrulline# and antio+idants# can
abrogate the state of o+idative stress and reverse the progression of atherosclerosis. This
approach may have clinical utility in the treatment of atherosclerosis in humans.
http://www.ncbi.nlm.nih.gov/pubmed/.F.EG99-
http://www.pnas.org/content/.3,/-9/.-F9..long
/eneficial role of vitamin C in protecting endothelial cell metaolism
Tumor necrosis alpha 7T0K-a8 has a damaging effect on the cells lining the artery# which
when damaged elicits inflammation and clot formation. Jitamin * 7(scorbic acid8 is able to
counter the damaging effect of T0K-a on the endothelium.
Ascoric acid locks the growth inhiitory effect of tumor necrosis factor-alpha on endothelial cells.
/ource: ;+p Aiol 1ed 71aywood8. ,33- 5ul6,,97G8:9EE-FE.
(uthor: /aeed "%# >eng T# 1etL *0.
(ffiliation: Daboratory of Jascular Aiology# 2ivision of 1edicinal Aiochemistry# 0orth
/hore-Dong )sland 5ewish "esearch )nstitute# 1anhasset# 0ew Yor& ..3-3# !/(.
(bstract: )mpaired endothelial cell proliferation has been proposed to be an early# critical
defect contributing to the development of atherosclerosis. "ecent studies show that high
plasma tumor necrosis factor 7T0K8-alpha levels and low serum ascorbic acid 7((8 levels
correlate with atherosclerosis severity. (dditionally# (( has been reported to have potential
beneficial effects in preventing atherosclerosis. Aased on these studies# we investigated the
role of (( 7I or =.m18 on T0K-alpha-mediated vascular endothelial cell growth inhibition
in vitro. )n accordance with previous reports# we found that T0K-alpha alone inhibited
endothelial cell proliferation. Kurther studies revealed that (( alone enhanced endothelial cell
proliferation and that (( bloc&ed endothelial cell growth inhibition induced by T0K-alpha.
Ay contrast# we observed no effect of (( on endothelial cell activation or nuclear entry of
nuclear factor-&appaA in response to T0K-alpha. The protective effect of (( on endothelial
cell proliferation was not simply the result of its antio+idant activity but did correlate with
collagen )J e+pression by endothelial cells. (( pre-treatment of proliferating endothelial
cells promoted retinoblastoma protein 7"b8 phosphorylation and decreased pE- levels when
compared to untreated cells. Kurthermore# the addition of (( to T0K-alpha-treated
proliferating endothelial cells bloc&ed both the inhibition of retinoblastoma protein
phosphorylation and enhanced pE- e+pression induced by T0K-alpha. *onsistent with these
results# we found that (( protects endothelial cells against T0K-alpha-induced apoptosis.
These studies highlight the potential therapeutic role of (( in promoting endothelial cell
proliferation during inflammatory conditions# such as atherosclerosis and cardiovascular
disease.
http://www.ncbi.nlm.nih.gov/pubmed/.,9GF-3F
http://www.ebmonline.org/cgi/content/full/,,9/G/9EE
/enefits of vitamin C in 0ype ** Diaetes patients
, grams oral ascorbic acid daily significantly increase forearm blood flow in patients with
diabetes mellitus and coronary artery disease. 2iabetes mellitus is &nown to have many
consequences including atherosclerosis and higher o+idative damage.
Vascular endothelium and inflammatory process! in patients with comined 0ype 1 diaetes mellitus and
coronary atherosclerosis: the effects of vitamin C.
/ource: 2iabet 1ed. ,33: 5un6,.7F8:EE,-9.
(uthor: (ntoniades *# Tousoulis 2# Tountas *# Tentolouris *# ToutouLa 1# Jasiliadou *#
Tsioufis *# ToutouLas ># /tefanadis *.
(ffiliation: *ardiology 2epartment# (thens !niversity 1edical /chool# Creece.
(bstract: ()1/: Type , diabetes mellitus 7218 and coronary artery disease 7*(28 are both
associated with endothelial dysfunction and elevated o+idative and inflammatory state. %e
e+amined the effect of vitamin * on endothelial function and levels of soluble vascular cell
adhesion molecule 7sJ*(1-.8# interleu&in-F 7)D-F8 and tumour necrosis factor 7T0K-alpha8#
in 21 patients with or without *(2 and in non-diabetic sub<ects. 1;T=2/: Thirty-seven
patients with 21 H *(2# .G patients with 21 without *(2 and ,. non-diabetic sub<ects
were divided into groups receiving vitamin * , g/day or no anti-o+idant for : wee&s. Korearm
blood flow was determined using venous occlusion gauge-strain plethysmography. Korearm
vasodilatory response to reactive hyperemia was considered as inde+ of endothelium-
dependent dilation. ";/!DT/: Aaseline levels of )D-F and T0K-alpha were significantly
higher in patients with 21 H *(2 compared with patients with 21 7> I 3.3.8 or non-
diabetic sub<ects 7> I 3.3.8. )D-F and T0K-alpha levels were also higher in 21 compared
with non-diabetic sub<ects 7> I 3.3E8. sJ*(1-. levels were lower in non-diabetic controls
compared with 21 H *(2 7> I 3.3E8 or 21 7> I 3.3E8. "eactive hyperaemia was higher in
non-diabetic controls compared with 21 H *(2 7> I 3.33.8 or 21 7> I 3.33.8. Jitamin *
significantly increased reactive hyperaemia only in the 21 H *(2 group# while it had no
effect on serum levels of sJ*(1-.# T0K-alpha and )D-F in any of the groups.
*0*D!/)0/: Type , diabetes mellitus is associated with impaired endothelial function
and increased levels of T0K-alpha# )D-F and sJ*(1-.# especially in patients with 21 and
*(2. Jitamin * significantly increased forearm vasodilatory response to reactive hyperaemia
only in patients with combined 21 and *(2.
http://www.ncbi.nlm.nih.gov/pubmed/.E.E:4-9
/enefits of vitamins + and C in the vascular system are associated with their effects on
extracellular matrix
This scientific review summariLes the role of vitamins ; and * on the synthesis and structure
of connective tissue of the blood vessel walls# essential for ptimum vascular wall function as
well as in the repair of atherosclerotic lesions during disease development.
)egulatory role of vitamins + and C on extracellular matrix components of the vascular system.
/ource: 1ol (spects 1ed. ,33G ct-2ec6,97E-F8:E3G--G.
(uthor: Jillacorta D# (LLi (# Mingg 51.
(ffiliation: *ardiovascular "esearch *enter# !niversity of 1ichigan 1edical *enter# (nn
(rbor# 1) :9.34# !/(.
(bstract: The protective effect of vitamins ; 7alpha-tocopherol8 and * 7D-ascorbic acid8 in the
prevention of cardiovascular disease 7*J28 has been shown in a number of situations but a
secure correlation is not universally accepted. !nder certain conditions# both# D-ascorbic acid
and alpha-tocopherol can e+hibit antio+idant properties and thus may reduce the formation of
o+idiLed small molecules# proteins and lipids# which are a possible cause of cellular de-
regulation. =owever# non-antio+idant effects have also been suggested to play a role in the
prevention of atherosclerosis. Jitamin ; and * can modulate signal transduction and gene
e+pression and thus affect many cellular reactions such as the proliferation of smooth muscle
cells# the e+pression of cell adhesion and e+tracellular matri+ molecules# the production of
7,87-8 by 0(2>=-o+idase# the aggregation of platelets and the inflammatory response.
Jitamins ; and * may modulate the e+tracellular matri+ environment by affecting J/1*
differentiation and the e+pression of connective tissue proteins involved in vascular
remodeling as well as the maintenance of vascular wall integrity. This review summariLes
individually the molecular activities of vitamins ; and * on the cells within the connective
tissue of the vasculature# which are centrally involved in the maintenance of an intact vascular
wall as well as in the repair of atherosclerotic lesions during disease development.
http://www.ncbi.nlm.nih.gov/pubmed/.GF,::.4
Clinical study indicates that vitamin C can prevent vascular in$ury caused y oxidative
stress
)schemia-reperfusion 7obstructing blood flow and restoring it8 is an event that is very
damaging in the case of heart attac&# in which interrupted blood flow by a blood clot or a
plaque is restored by surgical or chemical means. )ronically# restoring vital blood flow after a
period of blood starvation causes further cellular and tissue damage# and whole fields of study
are dedicated to preventing it. This clinical study shows that vitamin * 7(scorbic acid8 is able
to reverse the damage done to the dilation function of arteries e+posed to ischemia-
reperfusion in<ury.
*ntra-arterial vitamin C prevents endothelial dysfunction caused y ischemia-reperfusion
/ource: (therosclerosis. ,339 1ar6.4G7.8:-9--4..
(uthor: >leiner 5# /challer C# 1ittermayer K# 1arsi& *# 1ac(llister "5# Bapiotis /# Miegler
/# Kerlitsch (# %olLt 1.
(ffiliation: 2epartment of *linical >harmacology# 1edical !niversity of Jienna# (ustria.
(bstract: A5;*T)J;: )schemia-reperfusion 7)"8 in<ury causes tissue in<ury and endothelial
dysfunction. There is evidence that o+idative stress plays an important role. 1;T=2/: %e
tested if )"-induced endothelial dysfunction could be prevented by administration of the
antio+idant vitamin *. Twenty-si+ healthy male sub<ects and eight male patients with
peripheral arterial disease 7>(28 were enrolled in this randomised placebo-controlled study.
Korearm blood flow 7KAK8 measurements in response to the vasodilators acetylcholine 7(*h6
endothelium-dependent agonist8 or nitroglycerin 70TC6 endothelium-independent8 were
performed before and after forearm ischemia for ,3 min. KAK responses were reassessed
during reperfusion with intra-arterial co-administration of ,: mg/min vitamin * or placebo. )n
si+ volunteers responses to the 0-synthase inhibitor 0-monomethyl-D-arginine 7D-011(8
were also assessed before and after ischemia with and without vitamin *. ";/!DT/: (*h-
induced vasodilation was blunted in sub<ects receiving placebo after reperfusion 7pI3.3E
versus baseline8. (dministration of vitamin * completely prevented impaired responsiveness.
0TC-induced vasodilation was not affected by reperfusion or vitamin *. This finding was
consistent in patients with >(2 and impaired endothelial function# where local vitamin *
infusion restored KAK reactivity to (*h before and after )" in<ury 7pI3.3E versus baseline8.
(gain# 0TC-induced vasodilation was not affected. Alunted D-011( responses seen during
reperfusion could be completely reversed by vitamin *. *0*D!/)0/: ur data indicate
that )"-induced vascular in<ury can be prevented by administration of antio+idants.
http://www.ncbi.nlm.nih.gov/pubmed/.GF:E99.
http://www.atherosclerosis-<ournal.com/article//33,.-4.E373G833-4F-F/abstract
Clinical trial indicates that intake of vitamins C and + improves endothelial function in
children with hyperlipidemia.
( randomiLed# double-blind# placebo-controlled trial in .E children with high cholesterol
7familial hypercholesterolemia8 and lipid disorders shows that daily inta&e of vitamin *
7E33mg/d8 and ; 7:33 )!/d8 for F wee&s improves endothelial function thereby decreasing a
ris& for atherosclerosis.
Antioxidant vitamins C and + improve endothelial function in children with hyperlipidemia: +ndothelial
Assessment of )isk from "ipids in 2outh 3+A)"24 0rial.
/ource: *irculation. ,33- /ep ,6.39748:.3E4-F-.
(uthor: ;ngler 11# ;ngler 1A# 1alloy 15# *hiu ;Y# /chloetter 1*# >aul /1# /tuehlinger
1# Din BY# *oo&e 5># 1orrow 52# "id&er >1# "ifai 0# 1iller ;# %itLtum 5D# 1ietus-
/nyder 1.
(ffiliation: !niversity of *alifornia# /an Krancisco# , Boret %ay# "m 0F-.# /an Krancisco#
*alif 4:.:--3F.3# !/(. marguerite.engler@nursing.ucsf.edu
(bstract: A(*BC"!02: =yperlipidemia is associated with endothelial dysfunction# an
early event in atherosclerosis and predictor of ris& for future coronary artery disease.
;pidemiological studies suggest that increased dietary inta&e of antio+idants reduces the ris&
of coronary artery disease. The purpose of this study was to determine whether antio+idant
vitamin therapy improves endothelial function and affects surrogate biomar&ers for o+idative
stress and inflammation in hyperlipidemic children. 1;T=2/ (02 ";/!DT/: )n a
randomiLed# double-blind# placebo-controlled trial# the effects of antio+idant vitamins * 7E33
mg/d8 and ; 7:33 )!/d8 for F wee&s and the 0ational *holesterol ;ducation >rogram /tep ))
70*;>-))8 diet for F months on endothelium-dependent flow-mediated dilation 7K128 of the
brachial artery were e+amined in .E children with familial hypercholesterolemia 7K=8 or the
phenotype of familial combined hyperlipidemia 7K*=8. (ntio+idant vitamin therapy
improved K12 of the brachial artery compared with baseline 7>I3.33.8 without an effect on
biomar&ers for o+idative stress 7autoantibodies to epitopes of o+idiLed D2D# K,-isoprostanes#
9-hydro+y-,$-deo+yguanosine8# inflammation 7*-reactive protein8# or levels of asymmetric
dimethylarginine# an endogenous inhibitor of nitric o+ide. *0*D!/)0/: (ntio+idant
therapy with vitamins * and ; restores endothelial function in hyperlipidemic children. ;arly
detection and treatment of endothelial dysfunction in high-ris& children may retard the
progression of atherosclerosis.
http://www.ncbi.nlm.nih.gov/pubmed/.,4.,93G
http://circ.aha<ournals.org/cgi/content/full/.39/4/.3E4
+5C5 from green tea improves various metaolic factors associated with
atherosclerosis in high fat diets
This study conduced in rats fed of a diet e+tremely high in atherosclerotic lipids show that
intraperitoneal administration of ;C*C# a powerful polyphenol in green tea was able to
reduce the blood lipid levels and lower o+idative stress in red blood cells and heart muscle
despite of pro-atherogenic diet.
+pigallocatechin gallate improves serum lipid profile and erythrocyte and cardiac tissue antioxidant
parameters in 6istar rats fed an atherogenic diet.
/ource: Kundam *lin >harmacol. ,339 5un6,,7-8:,GE-9:.
(uthor: "amesh ;# ;lancheLhian "# /a&thivel 1# 5aya&umar T# /enthil Bumar "/# Ceraldine
># Thomas >(.
(ffiliation: 2epartment of (nimal /cience# /chool of Dife /ciences# Aharathidasan
!niversity# Tiruchirappalli F,3 3,:# Tamil 0adu# )ndia.
(bstract: +idative stress is believed to contribute to the pathogenesis of
hypercholesterolaemic atherosclerosis6 hence# various antio+idant compounds are being
evaluated for potential anti-atherogenic effects. The present study assessed the efficacy of
epigallocatechin gallate 7;C*C8# an antio+idant component of the plant *amellia sinensis# in
improving serum lipid profile and antio+idant parameters in erythrocytes and cardiac tissue in
rats fed an atherogenic diet. )n male albino %istar rats fed an atherogenic diet for -3 days#
significantly increased serum levels of total cholesterol# triglycerides and lipoprotein
cholesterol fractions and cardiac ris& ratio were noted# compared with levels in rats fed a
normal diet. )ntraperitoneal administration of ;C*C 7.33 mg/&g8 for G or .E days to the
atherogenic diet-fed rats resulted in significantly lower serum levels of total cholesterol#
triglycerides# low-density and very low density lipoprotein cholesterol fractions and a
significantly higher serum level of high-density lipoprotein cholesterol compared with levels
in atherogenic diet-fed# saline-treated rats. /ignificantly higher mean malondialdehyde levels
and significantly lower mean activities of antio+idant enLymes and mean levels of non-
enLymatic antio+idants occurred in atherogenic diet-fed rats compared with those fed a
normal diet. %hen atherogenic diet-fed rats received ;C*C treatment for G or .E days#
significantly lower mean levels of 12(# higher mean levels of non-enLymatic antio+idants
and higher mean activities of enLymatic antio+idants occurred# compared with those in saline-
treated rats. Thus# ;C*C appears to ameliorate disruptions of serum lipid profile and of
antio+idant parameters in erythrocyte and cardiac tissue of %istar rats fed an atherogenic diet6
these results may be relevant to treating human atherosclerosis.
http://www.ncbi.nlm.nih.gov/pubmed/.9:9E.:E
7olic Acid! .mega-3 7atty Acids! Arginine and antioxidant vitamins enhance positive
function of %itric oxide.
This study shows that the benefits of these micronutrients in cardiovascular health relate to
cellular mechanism of enhancing endogenous 0# a vasodilatory molecule. The author
suggest using a combination of these nutrients to enhance their positive effects.
7olic acid says %. to vascular diseases.
/ource: 0utrition. ,33- 5ul-(ug6.47G-98:F9F-4,.
(uthor: 2as !0.
(ffiliation: ;K( /ciences DD*# 0orwood# 1assachusetts# !/(. undurti@hotmail.com
(bstract: A5;*T)J;/: The possible lin& between folic acid or folate and
tetrahydrobiopterin 7=7:8A8# vitamin *# polyunsaturated fatty acids 7>!K(s8# and nitric o+ide
708# which may e+plain the beneficial actions of these nutrients in various vascular
conditions# was investigated. 1;T=2/: The literature pertaining to the actions of folic
acid/folate# =7:8A# vitamin *# >!K(s# and 0 was reviewed. ";/!DT/: )mpaired
endothelial 0 7e08 activity is an early mar&er for cardiovascular disease. 1ost ris& factors
for atherosclerosis are associated with impaired endothelium-dependent vasodilatation due to
reduced 0 production. Kolate not only reduces plasma homocysteine levels but also
enhances e0 synthesis and shows anti-inflammatory actions. )t stimulates endogenous
=7:8A regeneration# a cofactor necessary for e0 synthesis# inhibits intracellular supero+ide
generation# and thus enhances the half-life of 0. =7:8A in turn enhances 0 generation and
augments arginine transport into the cells. Kolic acid increases the concentration of omega--
>!K(s# which also enhance e0 synthesis. Jitamin * augments e0 synthesis by increasing
intracellular =7:8A and stabiliLation of =7:8A. )nsulin stimulates =7:8A synthesis and >!K(
metabolism# suppresses the production of proinflammatory cyto&ine tumor necrosis factor-
alpha and supero+ide anion# and enhances 0 generation. The ability of folate to augment
e0 generation is independent of its capacity to lower plasma homocysteine levels.
*0*D!/)0/: The common mechanism by which folic acid# =7:8A# vitamin *# omega--
fatty acids# and D-arginine bring about their beneficial actions in various vascular diseases is
by enhancing e0 production. =ence# it remains to be determined whether a <udicious
combination of folic acid# vitamins A.,# AF# and *# =7:8A# D-arginine# and omega-- fatty
acids in appropriate amounts may form a novel approach in the prevention and management
of various conditions such as hyperlipidemias# coronary heart disease# atherosclerosis#
peripheral vascular disease# and some neurodegenerative conditions.
http://www.ncbi.nlm.nih.gov/pubmed/.,9-.4F3
http://www.nutrition<rnl.com/article//3944-433G73,83.3::-:/abstract
*ntravenous Vitamin C and Vitamin + coated hemodialysis memrane reduce oxidative
damage and inflammation in patients undergoing hemodialysis.
=emodialysis prolongs the life of those with life-threatening renal failure. !nfortunately#
blood dialysis patients consequently suffer anemia and atherosclerosis from the procedure
which causes a huge .:-times increase in free radicals in the blood. Ay administering
intravenous vitamin * and coating the dialysis membrane with vitamin ;# o+idative
compounds in the plasma and o+idative damage in the blood were significantly reduced.
+ffects of vitamin C infusion and vitamin +-coated memrane on hemodialysis-induced oxidative stress.
/ource: Bidney )nt. ,33F Keb6F47:8:G3F-.:.
(uthor: Yang **# =su /># %u 1/# =su /1# *hien *T.
(ffiliation: Taipei *ity =ospital# =eping Aranch# and 2epartment of >hysiology# 0ational
Taiwan !niversity *ollege of 1edicine# Taipei# Taiwan.
(bstract: *hronic hemodialysis 7=28 patients manifest anemia and atherosclerosis with
associated o+idative stress. %e e+plored whether intravenous infusion of vitamin * 7J*8
and/or use of vitamin ; 7J;8-coated dialysis membrane could palliate =2-evo&ed o+idative
stress. ;ighty patients undergoing chronic =2 were enrolled and randomly assigned into four
groups: =2 with intravenous J* 7n=,38# =2 with J;-coated dialyLer 7n=,38# =2 with both
7n=,38# and =2 with neither 7n=,38. %e evaluated o+idative stress in blood and plasma#
erythrocyte methemoglobin/ferricyanide reductase 7red blood cells 7"A*8-1K"8 activity#
plasma methemoglobin# and pro-inflammatory cyto&ines in these patients. (ll patients
showed mar&ed increases 7.:-fold8 in blood reactive o+ygen species 7"/8 after =2. The
types of "/ were mostly hydrogen pero+ide# and in lesser amounts# ,U- and =*l. =2
resulted in decreased plasma J*# total antio+idant status# and "A*-1K" activity and
increased plasma and erythrocyte levels of phosphatidylcholine hydropero+ide 7>*=8 and
methemoglobin. )ntravenous J* significantly palliated =2-induced o+idative stress# plasma
and "A* levels of >*=# and plasma methemoglobin levels and preserved "A*-1K"
activity. The J;-coated dialyLer effectively prevented "A*s from o+idative stress# although
it showed a partial effect on the reduction of total "/ activity in whole blood. )n conclusion#
intravenous J* plus a J;-coated dialyLer is effective in palliating =2-evo&ed o+idative
stress# as indicated by hemolysis and lipid pero+idation# and by overe+pression of
proinflammation cyto&ines in =2 patients. !sing J;-coated dialyLer per se is# however#
effective in reducing lipid pero+idation and o+idative damage to "A*s.
http://www.ncbi.nlm.nih.gov/pubmed/.F-4E,E.
http://www.nature.com/&i/<ournal/vF4/n:/abs/E333.34a.html
"ong-term low intake of vitamin C increases the risk of cardiovascular diseases
ne of the pioneers of vitamin * research# 2r ;mil Cinter reviews and discusses the role and
cellular mechanisms of vitamin * in prevention of atherosclerosis.
Chronic vitamin C deficiency increases the risk of cardiovascular diseases.
/ource: Aratisl De& Disty. ,33G6.39748::.G-,..
(uthor: Cinter ;.
(ffiliation: >ublic =ealth (uthority of the /lova& "epublic# Aratislava# /lova&ia.
ginter.emil@mail.t-com.s&
(bstract: The studies on e+perimental animals 7guinea pigs# mon&eys# fish8 have confirmed
the important role of ascorbic acid deficiency in the development of hypercholesterolemia and
atherosclerosis# but the clinical e+perience is not quite uniform. 1etaanalyses of randomiLed
controlled trials performed on sub<ects without established vitamin *-deficiency conclud that
the evidence of the presence or absence of benefits derived from the ability of ascorbic acid to
prevent cardiovascular diseases is not sufficient. This review is an outline of numerous
clinical# epidemiological and prospective studies that have found a positive role of vitamin *
in the prevention of atherosclerosis. )f we admit the possibility that vitamin * deficiency is a
significant ris& factor of atherogenesis# due to ethical reasons it is impossible to perform long-
term controlled trials on sub<ects with proved vitamin * deficiency# to recommend them not
to change their nutrition and lifestyle# and to administer placebo to the control group.
Therefore the proof of atherogenic effect of chronic vitamin * deficiency is limited to indirect
evidence only. )n this review many new data on the positive effects of ascorbic acid on human
cardiovascular system are summariLed and the mechanisms of its protective influence on
blood vessels are discussed 7Kig.E# "ef. :E8.
http://www.ncbi.nlm.nih.gov/pubmed/.9,,E:9,
http://www.bm<.s&/,33G/.3934-34.pdf
"ow dietary intake of eta-carotene! alpha-tocopherol and ascoric acid is associated
with increased inflammatory and oxidative stress
/tudy conducted among /wedish men 7average G3 years old8 over G years indicate that
various metabolic mar&ers associated with atherosclerosis and heart disease were lower in
those with a higher dietary inta&e of antio+idant vitamins including vitamin * over a long
period of time.
"ow dietary intake of eta-carotene! alpha-tocopherol and ascoric acid is associated with increased
inflammatory and oxidative stress status in a 'wedish cohort.
/ource: Ar 5 0utr. ,334 5un6.3.7.,8:.GGE-9,.
(uthor: =elmersson 5# (rnlVv 5# Darsson (# Aasu /.
(ffiliation: 2epartment of "esearch and 2evelopment# *ounty *ouncil of CWvleborg/!ppsala
!niversity# CWvle =ospital# CWvle /;-93. 9G# /weden.
(bstract: Kruit and vegetable consumption has been associated with a reduced ris& of several
diseases including *J2. ( part of these effects seen could be lin&ed to anti-inflammatory and
antio+idative effects# although this has not been thoroughly investigated. The present study
was designed to investigate the effects of the dietary inta&e of beta-carotene# alpha-tocopherol
and ascorbic acid on in vivo biomar&ers of inflammation 7>CK,alpha# high-sensitive *-
reactive protein 7hs*">8 and )D-F formation8 and o+idative stress 7K,-isoprostane formation8#
the two important factors associated with accelerated atherosclerosis. The dietary inta&e of
G3: participants in the !ppsala Dongitudinal /tudy of (dult 1en 7!D/(18 at age G3 years
was registered and inflammatory and o+idative stress biomar&ers were quantified G years
later. The registered dietary inta&es of ascorbic acid and alpha-tocopherol were negatively
associated linearly and in quartiles with both >CK,alpha# hs*"># )D-F and K,-isoprostanes#
where ascorbic acid inta&e generally was more strongly associated. 2ietary inta&e of beta-
carotene was only significantly negatively associated with K,-isoprostanes. )n conclusion# the
present study is the first to suggest that the inta&e of food rich in antio+idants is associated
with reduced cyclo-o+ygenase- and cyto&ine-mediated inflammation and o+idative stress at G
years of follow-up. These associations could be lin&ed to the beneficial effects of fruit and
vegetables observed on *J2.
http://www.ncbi.nlm.nih.gov/pubmed/.43G49-9
"ower antioxidant vitamin levels indicate higher inflammation in coronary artery
disease patients.
There is an association between atherosclerosis# o+idation damage# and lower levels of
antio+idant vitamins in the bloodstream. This study also shows higher level of immune cell
activation in coronar artery disease patients. Aecause o+idative stress is increased with
chronic immune cell activation of any &ind# it is important to replenish these antio+idant
vitamins in order to prevent additional o+idative damage and &eep the immune system
functioning effectively.
*nverse association etween serum concentrations of neopterin and antioxidants in patients with and
without angiographic coronary artery disease.
/ource: (therosclerosis. ,334 Keb6,3,7,8:E:--4.
(uthor: 1urr *# %in&lhofer-"oob A1# /chroec&snadel B# 1aritschnegg 1# 1angge =#
AVhm A# %in&elmann A"# 1WrL %# Kuchs 2.
(ffiliation: 2ivision of Aiological *hemistry# Aiocenter# )nnsbruc& 1edical !niversity#
)nnsbruc&# (ustria.
(bstract: 0eopterin is released from human monocyte-derived macrophages upon stimulation
with interferon-gamma and is a sensitive indicator for cellular immune activation.
Kurthermore# reactive o+ygen species 7"/8 are produced in case of immune activation and
inflammation. )n a cross-sectional approach# plasma concentrations of neopterin and of
antio+idant compounds and vitamins were compared in .:F- patients investigated by
coronary angiography# which were recruited within the D!dwigshafen ")s& and
*ardiovascular =ealth 7D!")*8 study. /erum neopterin concentrations were higher in
patients with coronary artery disease 7*(26 meanH/-/.2.: 9.GH/-G.- nmol/D8 compared to
controls 7G.:H/-E.3 nmol/D6 %elch$s t-test: pI3.33.8. 1ean concentrations of ascorbic acid
7pI3.333.8# gamma-tocopherol 7pI3.3E8# lycopene 7pI3.33.8# luteinHLea+anthin 7pI3.3E8#
alpha-carotene 7pI3.3E8 and beta-carotene 7pI3.3E8 were lower in *(2 than in controls.
0eopterin concentrations correlated with *(2-score 7r7s8=3..EF6 pI3.333.8 and inversely
with antio+idants lycopene 7r7s8=-3.,GG6 pI3.333.8 and luteinHLea+anthin 7r7s8=-3..GE6
pI3.333.8 levels and with vitamins ascorbic acid 7r7s8=-3.,3G6 pI3.333.8 and alpha-
tocopherol 7r7s8=-3..3E6 pI3.333.8. The study demonstrates that higher neopterin production
is associated with lower concentrations of antio+idant compounds in patients at ris& for
atherosclerosis. "esults suggest that lower concentrations of antio+idant compounds may
relate to higher grade of chronic immune activation in patients.
http://www.ncbi.nlm.nih.gov/pubmed/.9EEF333
http://www.atherosclerosis-<ournal.com/article//33,.-4.E3739833--3-:/abstract
.ral Vitamin C and + reduce stickiness of "D" to artery walls.
)n addition to XTeflon-coatingY effects of lysine and proline proposed by 2r "ath as a way to
prevent stic&iness of lipoproteins and their accumulation in the artery wall there are other
nutritional approaches to combat other Xstic&y moleculesY that cause lipoprotein infiltration
and accumulation inside the artery. )n this case# vitamin * and ; diminish the affinity of D2D
to vascular wall components in both smo&ers and non-smo&ers.
8Decrease of affinity etween arterial proteoglycans and "D" isolated from smokers and non-smokers
with vitamin + and C administration9
/ource: )nvest *lin. ,33: 5un6:E7,8:.E4-G:.
(uthor: AarZn D# "omero-Jecchione ;# DZpeL K.
(ffiliation: *[tedra de Aioqu\mica# Daboratorio de Dipoprote\nas# ;scuela de 1edicina 5os]
1ar\a Jargas# Kacultad de 1edicina# !niversidad *entral de JeneLuela# *aracas# JeneLuela.
publique@cantv.net
(bstract: D2D interaction with arterial proteoglycans and its o+idative modification is closely
related to atherosclerosis. The ob<ective of the present study was to e+amine the effect of the
individual administration of vitamin ; and a combination of vitamin ; and * on D2D affinity
for arterial proteoglycans in smo&ers and non-smo&ers sub<ects. Twenty smo&ers and ten non-
smo&ers healthy sub<ects received by the oral route placebos of vitamins ; and * for .E days6
then vitamin ; 7:33 mg/d8 for -3 days and finally vitamin ; plus vitamin * 7.333 mg/d8
during the following -3 days. 2uring the vitamin ; supplementation period# the affinity of
D2D for arterial proteoglycans decreased .4.-O in smo&ers and ,E.,O in non-smo&ers. %hen
the sub<ects received vitamin ; plus vitamin *# the affinity of D2D for arterial proteoglycans
decreased ,E.FO and -3..O in smo&ers and non-smo&ers respectively. )n conclusion#
simultaneous administration of vitamins ; and * showed a synergistic effect to diminish the
affinity of the D2D by arterial proteoglycans# that was greater than caused by the
administration of vitamin ; alone. These finding suggest a potential antiatherogenic effect of
both antio+idant vitamins.
http://www.ncbi.nlm.nih.gov/pubmed/.E,..49-
#lant components comined with vitamins C and + decrease insulin resistance and
atherosclerotic changes in aged rats with chronic kidney failure
This animal study conducted on aging rats with chronic &idney failure has implications for
human health. The authors of the study conclude that plant components 7*atechin8 and
vitamins ; and * supplementation can decrease o+idative stress associated with &idneyl
failure# and counteract insulin resistance# elevated blood pressure and other changes
associated with atherosclerosis in the elderly.
Catechin comined with vitamins C and + ameliorates insulin resistance 3*)4 and atherosclerotic changes
in aged rats with chronic renal failure 3C)74.
/ource: (rch Cerontol Ceriatr. ,339 5an-Keb6:F7.8:,E--4.
(uthor: Borish ((# (rafah 11.
(ffiliation: 2epartment of >hysiology 7,48# Kaculty of 1edicine# Bing /aud !niversity# >
Ao+ ,4,E# "iyadh ..:F.# /audi (rabia. iaida&orish@hotmail.com
(bstract: (ging is an inevitable biological process associated with increased o+idative stress
and accumulation of asymmetric dimethylarginine 7(21(8 a &nown endogenous inhibitor of
nitric o+ide synthase. (therosclerosis and )" constitute ma<or ris& factors for cardiovascular
mortality in elderly with chronic &idney disease 7*B28. %e investigated the impact of
catechin# vitamins ; and * supplementation on insulin sensitivity# redo+ state# (21(# nitrate
and nitrite 707,87-8/07-87-88 levels and histological picture of heart and large blood vessels
of aged rats with *"K. Kindings of the present study revealed that aging in rats is associated
with hyperinsulinemia# hyperlipidemia# )" indicated by higher homeostasis model assessment
7=1(8-inde+# increased lipid pero+idation product malondialdehyde 712(8# (21(# and
blood pressure 7A>8# but decreased antio+idant capacity and 07,87-8/07-87-8 levels. *"K
e+aggerated all these findings and caused thic&ened intima of carotid arteries and myocardial
hypertrophy. Treatment with catechin# vitamins ; and * increases the antio+idant capacity
and 07,87-8/07-87-8 production but# decreases 12(# (21( and A> levels. (lso it &eeps
insulin sensitivity and normal intima/media thic&ness of carotid arteries. %e conclude that
decreased nitric o+ide 708 availability due to (21( accumulation may be responsible for
)" and associated atherosclerotic changes in aged rats with *"K. *atechin# vitamins ; and *
supplementation may moderate o+idative stress of renal failure# prevent (21(
accumulation# and counteract )" and atherosclerotic changes in the elderly.
http://www.ncbi.nlm.nih.gov/pubmed/.G:.9439
'tudy conducted among young adults shows increased risk of coronary calcifications
with low vitamin C levels.
(nalysis of the data from ,#F-G (frican-(merican and %hite men and women aged .9--3
showed that low to marginally low vitamin * levels in men but not women predict coronary
artery calcification. *alcification of the coronary arteries is an indicator of the advancement
of atherosclerosis. /ites of calcification in the coronary arteries are prone to generation of
thrombosis and consequent heart attac&.
)elation of ascoric acid to coronary artery calcium: the Coronary Artery )isk Development in 2oung
Adults 'tudy.
/ource: (m 5 ;pidemiol. ,33: 1ar .E6.E47F8:E9.-9.
(uthor: /imon 5(# 1urtaugh 1(# Cross 12# Doria *1# =ulley /A# 5acobs 2" 5r.
(ffiliation: Ceneral )nternal 1edicine /ection 7...(.8# 1edical /ervice# Jeterans (ffairs
1edical *enter and !niversity of *alifornia# :.E3 *lement /treet# /an Krancisco# *( 4:.,.#
!/(. <asimon@itsa.ucsf.edu
(bstract: (scorbic acid is an antio+idant nutrient possibly related to the development of
atherosclerosis. To e+amine the relation between ascorbic acid and coronary artery calcium#
an indicator of subclinical coronary disease# the authors analyLed data from ,#F-G (frican-
(merican and %hite men and women aged .9--3 years at baseline who were enrolled in the
*oronary (rtery "is& 2evelopment in Young (dults 7*("2)(8 /tudy 7.49E-,33.8.
>articipants completed diet histories at enrollment and year G# and plasma ascorbic acid levels
were obtained at year .3. *oronary artery computed tomography was performed at year .E.
The authors calculated odds ratios in four biologically relevant plasma ascorbic acid
categories# ad<usting for possible confounding variables. %hen compared with men with high
plasma ascorbic acid levels# men with low levels to marginally low levels had an increased
prevalence of coronary artery calcium 7multivariate odds ratio = ,.F9# 4EO confidence
interval: ..-.# E.:98. (mong women# the association was attenuated and nonsignificant
7multivariate odds ratio = ..E3# 4EO confidence interval: 3.E9# -.9E8. (scorbic acid inta&es
from diet alone and diet plus supplements were not associated with coronary artery calcium.
Dow to marginally low plasma ascorbic acid levels were associated with a higher prevalence
of coronary artery calcium among men but not among women.
http://www.ncbi.nlm.nih.gov/pubmed/.E33-4F,
http://a<e.o+ford<ournals.org/cgi/content/full/.E4/F/E9.
'upplementation with vitamins C and + improves arterial flexiility and function in
patients with high lood pressure
This randomiLed# double-blind# placebo-controlled study in -3 men suffering from high blood
pressure revealed that supplementation with vitamin * 7. g8 and vitamin ; 7:33 )!8 for 9
wee&s decrease o+idative stress and blood vessel stiffness a hallmar& of high blood pressure.
'upplementation with vitamins C and + improves arterial stiffness and endothelial function in essential
hypertensive patients.
/ource: (m 5 =ypertens. ,33G (pr6,37:8:-4,-G.
(uthor: >lantinga Y# Chiadoni D# 1agagna (# Ciannarelli *# KranLoni K# Taddei /# /alvetti
(.
(ffiliation: 2epartment of )nternal 1edicine# !niversity of >isa# >isa# )taly.
(bstract: A(*BC"!02: ;ssential hypertension is characteriLed by endothelial
dysfunction# arterial stiffness# and increased o+idative stress. %e evaluated the effect of short-
term combined treatment with the antio+idants vitamins * and ; on endothelial function#
arterial stiffness# and o+idative stress in untreated essential hypertensive patients.
1;T=2/: ( randomiLed# double-blind# placebo-controlled# crossover study design was
used to assign -3 male essential hypertensive patients to either vitamin * 7. g8 and vitamin ;
7:33 )!8 or placebo for 9 wee&s. ;ndothelium-dependent response was assessed as flow-
mediated dilation 7K128 of the brachial artery. (rterial stiffness was assessed as central pulse
wave velocity 7>%J8 and augmentation inde+ 7()+8. >lasma mar&ers of o+idative stress and
antio+idant status were measured. ";/!DT/: (fter vitamin supplementation# K12 was
significantly improved. *entral >%J was significantly reduced# while ()+ tended to
decrease. >lasma vitamin levels and antio+idant capacity increased significantly. Devels of
o+idative stress decreased. *hanges in central >%J were related to changes in levels of
o+idative stress. *0*D!/)0/: *ombined treatment with vitamins * and ; has beneficial
effects on endothelium-dependent vasodilation and arterial stiffness in untreated# essential
hypertensive patients. This effect is associated with changes in plasma mar&ers of o+idative
stress.
http://www.ncbi.nlm.nih.gov/pubmed/.G-9F-:E
'ynergistic effect of %-acetylcysteine! Ascoric acid! and )esveratrol can protect
macrophage death
The combination of these nutrients had much higher effectiveness than their individual
compounds in preventing the death of macrophages by a to+ic substance# triacylglycerol.
=ealthy macrophage function is important in reducing atherosclerosis and arterial
inflammation. This study confirms nutrient synergy approach pioneered by 2r "ath "esearch
)nstitute is allowing to achieve superior physiological effects with moderate nutrient doses
and preserve metabolic cellular balance.
(echanism underlying oxidative stress-mediated lipotoxicity: exposure of :;;<.1 macrophages to
triacylglycerols facilitates mitochondrial reactive oxygen species production and cellular
necrosis.
/ource: Kree "adic Aiol 1ed. ,33E 1ay .6-9748:.,,.--3.
(uthor: (ronis (# 1adar M# Tirosh .
(ffiliation: /chool of 0utritional /ciences# )nstitute of Aiochemistry# Kood /cience and
0utrition# Kaculty of (gricultural# Kood and ;nvironmental Quality /ciences# The =ebrew
!niversity of 5erusalem# "ehovot GF.33# )srael.
(bstract: The aim of this study was to elucidate death pathways in macrophages resulting
from e+posure to triacylglycerols 7TC8# mechanisms which may be relevant to the
development of atherosclerosis. ( commercial TC emulsion 7lipid emulsion# D;6 3..-..E mg
lipids/ml8 was added to 5GG:., cells in culture. %ithin the first ,: h after TC treatment#
cellular reactive o+ygen species 7"/8 levels were strongly elevated and basal caspase--
activity was attenuated. )n contrast# after :9 h# "/ production was arrested. TC-mediated
"/ production was demonstrated to be via mitochondrial comple+ . of the electron-transfer
chain since the inhibitor of comple+ . rotenone significantly attenuated the cellular "/
levels in TC-treated cells. The TC effect culminated in cell death# with no caspase--
activation. %e therefore evaluated the effect of TC on apoptotic cells showing high caspase
activity. TC induced elevated "/ levels and suppressed caspase-- in apoptotic cells
pretreated for ,: h with cyclohe+imide. 2ual staining with propidium iodide and (nne+in J
followed by flow cytometric analysis showed that TC facilitated cell death with clear necrotic
characteristics. To elucidate whether the necrotic cell death process is indeed o+idant
dependent# antio+idant protection was studied. Treatment with 0-acetylcysteine 70(*8 73.E
m18# ascorbic acid 73.E m18# and resveratrol 73., m18 protected against the TC lipoto+ic
effect# while# surprisingly# lipophilic antio+idants did not. The combination of 0(*# ascorbic
acid# and resveratrol# each at much lower concentrations# had a synergistic protective effect.
)n conclusion# we show here for the first time that e+posure to TC can directly regulate
lipoto+icity in macrophages by inducing mitochondria-mediated prolonged o+idative stress6
this# in turn# can inactivate the apoptotic caspase system# resulting in necrotic cell death which
can be prevented by specific antio+idants.
http://www.ncbi.nlm.nih.gov/pubmed/.E939:,3
0he derivative of a flavonoid! =uercetin! and Vitamin C reduce lood viscosity and have
other positive effects in patients with atherosclerosis.
(n age-related changes that come with atherosclerosis of the branching arteries of the nec&
and brain is the combination of headaches# fatigue# confusion# and diLLiness. This can lead to
stro&e. This "ussian group uses a simple combination of dihydroquercetin and vitamin * to
significantly improve this condition.
8Clinical efficacy of a novel hemorheological drug ascovertin in patients with vascular encephalopathy9
/ource: Mh 0evrol >si&hiatr )m / / Borsa&ova. ,33:6.3:7.,8:---G.
(uthor: >lotni&ov 1A# >lotni&ov 21# (lifirova J1# (liev )# 1aslov 1)u# Jasil$ev (/#
Tiu&av&ina 0(.
(ffiliation:
(bstract: >atients with stages ) and )) of vascular encephalopathy developing on the
bac&ground of atherosclerosis were treated with ascovertin during ,. days. (scovertin is a
comple+ of flavonoid dihydroquercetin and ascorbic acid. The study group included ,.
patients aged :E-FE years and a comparison group consisted of .3 age-matched patients un
treated with ascovertin. The ascovertin treatment relieved headache# reduced vertigo and
fatigability# improved cognitive functions. The reliable diminishing of whole blood viscosity
due to improvement of cellular rheology indices 7decrease of aggregation and increase of
erythrocyte deformability as well as decrease of indices of lipid pero+idation in erythrocyte
membrane and blood plasma8 was observed in the study group but not in the comparison one.
http://www.ncbi.nlm.nih.gov/pubmed/.E9:G-,:
Vitamin C and + may decrease risk of arterial pla&ues rupture and conse&uent
thromosis
The e+istence of atherosclerotic plaque alone does not predict death by heart attac& or stro&e.
)f the atherosclerotic occlusion is not too severe# and inflammatory cyto&ines &ept in chec&#
plaque rupture and thrombosis will not occur# and nearly normal functioning will continue.
Jitamin * and Jitamin ; are important in plaque stability by increasing collagen integrity
and decreasing its enLymatic degradation.
Antioxidant vitamins increase the collagen content and reduce ((#-- in a porcine model of
atherosclerosis: implications for pla&ue staili,ation.
/ource: (therosclerosis. ,33- 1ar6.FG7.8::E-E-.
(uthor: rbe 5# "odr\gueL 5(# (rias "# AelLunce 1# 0espereira A# >]reL-)lLarbe 1# "oncal
*# >[ramo 5(.
(ffiliation: (therosclerosis "esearch Daboratory# 2ivision of *ardiovascular
>athophysiology# /chool of 1edicine# !niversity of 0avarra# */)runlarrea .# *)K(# ;--.339
>amplona# /pain.
(bstract: 2egradation of e+tracellular matri+# particularly interstitial collagen# promotes
plaque instability and contributes to restenosis after vascular in<ury. %e have e+plored the
effects of vitamins * and ; on the collagen content and metalloproteinase-. 711>-.8
e+pression after angioplasty in hypercholesterolemic pigs. )liac angioplasty was performed on
.9 minipigs divided into three diet groups: a normal-cholesterol 70*8# a high-cholesterol
7=*8 and a high-cholesterol plus vitamins *H; 7=*J8. Kour wee&s later# after sacrifice# the
vascular collagen content and 11>-. protein e+pression# along with the plasma caseinolytic
activity and lipid pero+idation# were measured. 11>-. was also determined in arterial rings
stimulated with native low-density lipoproteins 7D2D8 isolated from e+perimental groups.
*holesterol-rich diet augmented plasma lipid pero+idation 7>I3.3E8# reduced the collagen
content and increased vascular 11>-. e+pression after in<ury 7>I3.3E8. ;nhanced
caseinolytic activity 7identified as 11>-.8 was also observed in =* plasma samples and in
supernatants from arterial rings incubated with =*-D2D. Jitamins * and ; mar&edly
increased neointimal collagen content 7>I3.3.8# reduced the hypercholesterolemia-induced
changes in vascular 11>-. 7>I3.3E8 and diminished plasma and e+ vivo caseinolytic
activity. Jitamins * and ; may help stabiliLe atherosclerotic plaque after angioplasty and
favor vascular remodeling by increasing collagen content and reducing vascular 11>-.
e+pression in porcine hypercholesterolemia.
http://www.ncbi.nlm.nih.gov/pubmed/.,F.9,FG
Vitamin C and + prevent death of the arterial lining y factors released into the
loodstream y heart attack.
(fter myocardial infarction 7heart attac&8# neutrophils and other inflammatory factors are
released that can damage the arteries in other locations# literally adding insult to in<ury.
Jitamin * and ; among other substances prevents the inner lining of the artery# the
endothelium# from death during this situation.
#revention of endothelial cell apoptosis induced y neutrophils and sera from patients with acute
myocardial infarction.
/ource: )nt 5 *ardiol. ,334 Keb ,. S;pub ahead of printT
(uthor: Krimmel /# =emmer *5# BenLler 5# !nverricht 1# )nce =# 0ienaber *(# "eisinger
;*.
(ffiliation: 2ivision of Tropical 1edicine and )nfectious 2iseases# 2epartment of 1edicine#
!niversity of "ostoc& 1edical /chool# Cermany.
(bstract: (poptosis of cardiomyocytes and vascular endothelial cells has been shown to
contribute to disease progression in coronary atherosclerosis# in myocardial infarction and in
ischemia-reperfusion in<ury. /era were obtained from .- patients with acute /T elevation
myocardial infarction and successful primary percutaneous coronary intervention. =uman
umbilical venous endothelial cells 7=!J;*s8 were incubated with sera from these patients
with or without addition of neutrophil granulocytes. T!0;D staining was performed# and
apoptotic cells were quantified with immunofluorescence microscopy. To reduce apoptotic
damage# ascorbic acid# vitamin ;# ulinastatin# or activated protein * were added to patients$
sera# with or without neutrophils# before incubation with endothelial cells. )ncubation of
endothelial cells with sera from patients increased the apoptosis rate significantly# compared
to sera from G healthy controls 7pI3.33.8. *o-incubation of endothelial cells with patients$
sera and neutrophils led to a further significant increase of apoptosis. The addition of ascorbic
acid# vitamin ;# or activated protein * significantly decreased apoptosis rates of endothelial
cells in the presence of neutrophils in vitro. (ntiapoptotic strategies may be relevant for the
therapy of acute coronary syndromes# since elevated leu&ocyte counts have been shown to be
associated with increased morbidity and mortality in coronary heart disease.
http://www.ncbi.nlm.nih.gov/pubmed/.4.4-:E:
Vitamin C Counteracts Arterial Dysfunction Caused y 7ree 7atty Acids.
Jarious studies indicate that elevated levels of non-esterified fatty acids impair endothelium-
dependent dilation of blood vessels. This study shows that this effect can be alleviated by
vitamin * and (rginine.
Vitamin C! diclophenac! and "-arginine protect endothelium-dependent vasodilation against elevated
circulating fatty acid levels in humans.
/ource: (therosclerosis. ,33- 1ay6.F97.8:FE-G,.
(uthor: /teer ># 1illg?rd 5# Aasu /# Dithell =# Jessby A# Aerne *# Dind D.
(ffiliation: 2epartment of 1edical /ciences/)nternal 1edicine# !niversity =ospital# /;-
GE.9E !ppsala# /weden. >eter./teer@medsci.uu.se
(bstract: (n acute elevation of circulating non-esterified fatty acids 70;K(s8 has previously
been shown to impair endothelium-dependent vasodilation 7;2J8. )n this study# we
investigated if local administration of vitamin * 7n=9# .9 mg/min8# D-arginine 7n=9# .,.E
mg/min8# or the cycloo+ygenase 7*^8 inhibitor diclophenac 7n=9# 3.E mg/min8 can
counteract the endothelial dysfunction seen during infusion of )ntralipid plus heparin 7n=.38.
;2J and endothelium-independent vasodilation 7;)2J8 were studied in the forearm after
local administration of methacholine chloride 71ch6 , and : microg/min8 and sodium
nitroprusside 7/0>6 E and .3 microg/min8. Korearm blood flow 7KAK8 was determined with
venous occlusion plethysmography. )ntralipid and heparin increased circulating 0;K( levels
sevenfold and impaired ;2J 7>I3.33. vs baseline8. *oncomitant administration of D-
arginine or diclophenac abolished the 0;K(-induced impairment in ;2J. *oncomitant
vitamin * administration actually improved ;2J 7>I3.3E vs baseline8. 0;K( elevation
increased ;)2J 7>I3.3.8# but this effect was not significant after D-arginine or diclophenac
infusions. )n conclusion# an acute elevation of circulating 0;K(s led to impaired ;2J.
(dministration of D-arginine# vitamin * or *^ inhibition abolished this effect# suggesting
that 0;K(s might interact with endothelial vasodilatory function through multiple
mechanisms.
http://www.ncbi.nlm.nih.gov/pubmed/.,G-,-99
http://www.atherosclerosis-<ournal.com/article//33,.-4.E373-8333,--F/abstract
Vitamin C effective in reducing inflammation in active and passive smokers
This randomiLed# double-blind# placebo-controlled# study in .F3 active and passive smo&ers
showed that , months inta&e of Jitamin * was superior to the antio+idant mi+ture in reducing
*-reactive proteins 7*">8 which is a mar&er of inflammation. )nterestingly# these benefits of
vitamin * supplementation were observed in people consuming more than : servings of fruits
and vegetables daily.
#lasma C-reactive protein concentrations in active and passive smokers: influence of antioxidant
supplementation.
/ource: 5 (m *oll 0utr. ,33: (pr6,-7,8:.:.-G.
(uthor: Aloc& C# 5ensen *# 2ietrich 1# 0or&us ;># =udes 1# >ac&er D.
(ffiliation: 2ivision of *ommunity =ealth and =uman 2evelopment# /chool of >ublic
=ealth# !niversity of *alifornia# Aer&eley# *alifornia 4:G,3# !/(. Cbloc&@ber&eley.edu
(bstract: A5;*T)J;: *-reactive protein 7*">8 may directly affect the progression of
atherosclerosis# and therefore# may be a target for reducing disease ris&. The ob<ective was to
determine whether antio+idant supplementation reduces plasma *"> in active and passive
smo&ers. 2;/)C0: "andomiLed# double-blind# placebo-controlled# parallel group trial with ,
months e+posure to study supplements. /;TT)0C: Aer&eley and a&land# *alifornia.
/!A5;*T/: =ealthy adult men and women# consuming I: daily servings of fruits and
vegetables# and who were actively or passively e+posed to cigarette smo&e. (nalysis was
limited to participants with detectable baseline *"> concentrations and no evidence of
inflammation associated with acute illness at baseline or follow-up as reflected in *">
elevations 7N or =.3.3 mg/D8. ( total of .-4- individuals were screened# ,.F randomiLed# ,3-
completed the study# and .F3 were included in the analysis. )0T;"J;0T)0/: >articipants
were randomiLed to receive a placebo or vitamin * 7E.E mg/day8 or antio+idant mi+ture 7per
day: E.E mg vitamin *# -G. mg alpha-tocopherol# .G. mg gamma-tocopherol# ,E, mg mi+ed
tocotrienols# and 4E mg alpha-lipoic acid8. 1easures of utcome: *hange in plasma *">
concentration. ";/!DT/: Jitamin * supplementation yielded a ,:.3O reduction 74EO
confidence interval# --9.4O to -E.EO# p = 3.3-F compared to control8 in plasma *"># whereas
the antio+idant mi+ture and placebo produced a nonsignificant :.GO reduction 7-,-.4O to
.4.-O8 and :.-O increase 7-.E..O to ,9.,O8# respectively. "esults were ad<usted for baseline
body mass inde+ and *"> concentrations. *0*D!/)0/: >lasma *"> itself may serve as
a potential target for reducing the ris& of atherosclerosis# and antio+idants# including vitamin
*# should be investigated further to confirm their *">-lowering and anti-inflammatory
effects.
http://www.ncbi.nlm.nih.gov/pubmed/.E3:GF93
http://www.<acn.org/cgi/content/full/,-/,/.:.
Vitamin C in protecting white lood cells 3macrophages4 against oxidative stress and
triggering their death cycle 3apoptosis4
(therosclerotic plaques are associated with the recruitment of white blood cells to the site of
arterial inflammation. This inflammation can be caused by several insults including o+idative
damage to cholesterol carrying lipoproteins-D2D. This in vitro study indicates that vitamin *
7(scorbic acid8 contributes to the survival of macrophages as they attempt to clear out and
resolve o+idiLed-D2D. )f the macrophages function normally# they have a chance to decrease
inflammation# allowing the artery to heal.
.xidi,ed lipoprotein induces the macrophage ascorate transporter 3'VC014: protection y intracellular
ascorate against oxidant stress and apoptosis.
/ource: (rch Aiochem Aiophys. ,334 1ay .E6:9E7,8:.G:-9,.
(uthor: *hi ^# 1ay 51.
(ffiliation: 2epartment of 1edicine# Janderbilt !niversity /chool of 1edicine# G:FE
1edical "esearch Auilding )J# 0ashville# T0 -G,-,-F-3-# !/(.
(bstract: To assess whether ascorbic acid decreases the cytoto+icity of o+idiLed human low
density lipoprotein 7o+D2D8 in cells involved in atherosclerosis# its interaction with o+D2D
was studied in murine "(%,F:.G macrophages. 1acrophages too& up ascorbate to
millimolar intracellular concentrations and retained it with little loss over .9h in culture.
*ulture of the macrophages with o+D2D enhanced ascorbate upta&e. This was associated with
increased e+pression of the ascorbate transporter 7/J*T,8# which was prevented by ascorbate
and by inhibiting the 0K-&appaA pathway. *ulture of "(%,F:.G macrophages with o+D2D
increased intracellular dihydrofluorescein o+idation and lipid pero+idation# both of which
were decreased by intracellular ascorbate. (scorbate also protected the cells against o+D2D-
induced cytoto+icity and apoptosis# but it did not affect macrophage accumulation of lipid
from o+D2D or o+D2D-induced increases in macrophage cyto&ine secretion. These results
suggest that ascorbate protects macrophages against o+D2D-induced o+idant stress and
subsequent apoptotic death without impairing their function.
http://www.ncbi.nlm.nih.gov/pubmed/.4,E:F9E
Vitamin + and C reduce atherosclerotic progression in patients with high cholesterol
levels.
This clinical study in E,3 patients 7smo&ers and nonsmo&ers8 with high cholesterol blood
levels shows that supplementation vith E33 mg of vitamin * daily for F years reduced the
thic&ening of the carotid artery walls in men and women by ,FO on average.
'ix-year effect of comined vitamin C and + supplementation on atherosclerotic progression: the
Antioxidant 'upplementation in Atherosclerosis #revention 3A'A#4 'tudy.
/ource: *irculation. ,33- Keb ,E6.3G7G8:4:G-E-.
(uthor: /alonen "1# 0yyssVnen B# Bai&&onen 5# >or&&ala-/arataho ;# Joutilainen /#
"issanen T=# Tuomainen T># Jal&onen J># "istonmaa !# Da&&a =1# Janharanta 1#
/alonen 5T# >oulsen =;6 (ntio+idant /upplementation in (therosclerosis >revention /tudy.
(ffiliation: "esearch )nstitute of >ublic =ealth# !niversity of Buopio# Kinland.
<u&&a.salonen@u&u.fi
(bstract: A(*BC"!02: /elf-selected supplementation of vitamin ; has been associated
with reduced coronary events and atherosclerotic progression# but the evidence from clinical
trials is controversial. )n the first - years of the (/(> trial# the supplementation with .-F )!
of vitamin ; plus ,E3 mg of slow-release vitamin * twice daily slowed down the progression
of carotid atherosclerosis in men but not women. This article e+amines the F-year effect of
supplementation on common carotid artery 7**(8 intima-media thic&ness 7)1T8.
1;T=2/ (02 ";/!DT/: The sub<ects were E,3 smo&ing and nonsmo&ing men and
postmenopausal women aged :E to F4 years with serum cholesterol N or =E.3 mmol/D 7.4-
mg/dD8# ::3 79:.FO8 of whom completed the study. (therosclerotic progression was assessed
ultrasonographically. )n covariance analysis in both se+es# supplementation reduced the main
study outcome# the slope of mean **(-)1T# by ,FO 74EO *)# E to :F# >=3.3.:8# in men by
--O 74EO *)# : to F,# >=3.3,:8 and in women by .:O 7not significant8. )n both se+es
combined# the average annual increase of the mean **(-)1T was 3.3.: mm in the
unsupplemented and 3.3.3 mm in the supplemented group 7,EO treatment effect# 4EO *)# ,
to :4# >=3.3-:8. )n men# this treatment effect was -GO 74E *)# : to F4# >=3.3,98. The effect
was larger in sub<ects with either low baseline plasma vitamin * levels or **( plaques.
Jitamin ; had no effect on =2D cholesterol. *0*D!/)0/: These data replicate our --
year findings confirming that the supplementation with combination of vitamin ; and slow-
release vitamin * slows down atherosclerotic progression in hypercholesterolemic persons.
http://www.ncbi.nlm.nih.gov/pubmed/.,F3343E
http://circ.aha<ournals.org/cgi/content/full/.3G/G/4:G