met vitamin c 4 april

8/17/2019 Met Vitamin C 4 April

1/73


2/73

OH

OO

HHO

HO

HO


3/73

Strong biopotencyStrong biopotencyaa WeakWeak biopotencybiopotencybb

Ascorbic acid 2- Ascorbic acid 2-OO--α α -glucoside-glucoside LL-Ascorbyl palmitate-Ascorbyl palmitate

6-Bromo-6-deoxy-6-Bromo-6-deoxy-LL-ascorbic acid-ascorbic acid LL-Ascorbyl-2-sulfate-Ascorbyl-2-sulfate

LL-Ascorbate 2-phosphate-Ascorbate 2-phosphate LL-Ascorbate--Ascorbate-OO-methyl ether-methyl ether

LL-Ascorbate 2-triphosphate-Ascorbate 2-triphosphate

aaMore than !" of antiscorbutic acti#ity of ascorbic acid$More than !" of antiscorbutic acti#ity of ascorbic acid$

bb Less than !" of antiscorbutic acti#ity of ascorbic acid$Less than !" of antiscorbutic acti#ity of ascorbic acid$


4/73

%elati#e biopotency%elati#e biopotency

&ompound '"(&ompound '"( Ascorbic acid )!! Ascorbic acid )!!

Ascorbyl-*6-diacetate )!! Ascorbyl-*6-diacetate )!!

Ascorbyl-6-palmitate )!! Ascorbyl-6-palmitate )!!

6-+eoxy-6-chloro-6-+eoxy-6-chloro-LL-ascorbic acid ,!-.-ascorbic acid ,!-.

+ehydroascorbic acid .!+ehydroascorbic acid .!

6-+eoxyascorbic acid //6-+eoxyascorbic acid //

Ascorbic acid 2-sulfate 0 Ascorbic acid 2-sulfate 0aa

1soascorbic acid 1soascorbic acid

LL-lucoascorbic acid /-lucoascorbic acid /

aa3his form is acti#e in fishes* 4hich ha#e an intestinal sulfohydrase that3his form is acti#e in fishes* 4hich ha#e an intestinal sulfohydrase thatliberated ascorbic acid5 it is inacti#e in guinea pigs* rhesus monkeys*liberated ascorbic acid5 it is inacti#e in guinea pigs* rhesus monkeys*and humans* 4hich lack the enyme$and humans* 4hich lack the enyme$


5/73

Fruits, vegetables and organ meats(liver, kidney)

Loss due to oxidation, in thepresence of O2, heat, metal ions,neutral and alkaline conditions.

ooking, loss due to heating and!ater

"uick heating can protect byinactivating of oxidases


6/73

FoodFood VitaminVitaminC(mg/100gC(mg/100g(( Food Vitamin C(mg/100g)Food Vitamin C(mg/100g)

FruitsFruits

Apple )!-/! Apple )!-/!

Banana )!Banana )!

&herry )!&herry )!

rapefruit 7!rapefruit 7!

ua#a /!!ua#a /!! 8a4thorn berries )6!-.!!8a4thorn berries )6!-.!!

Melons )/-//Melons )/-//

9range* lemon !9range* lemon !

:each ,-)7:each ,-)7

%aspberry ).-2%aspberry ).-2

%ose hips )!!!%ose hips )!!!

Stra4berry 7!-!Stra4berry 7!-!

3angerine /!3angerine /!Animal productsAnimal

products

Meats !-2Meats !-2

Li#er )!-7!Li#er )!-7!

;idney )!-7!;idney )!-7!

MilkMilk

&o4 )-2&o4 )-2

8uman /-68uman /-6

VegetablesVe

getables

Asparagus )-/! Asparagus )-/!

Bean )!-/!Bean )!-/!

Broccoli !-)!Broccoli !-)!

&abbage /!-6!&abbage /!-6!

&arrot -)!&arrot -)! &auliflo4er 6!-.!&auliflo4er 6!-.!

&elery )!&elery )!

&ollard greens )!!-)!&ollard greens )!!-)!

&orn )2&orn )2

;ale )2!-).!;ale )2!-).!

Leek )-/!Leek )-/!

9at* 4heat !9at* 4heat !

9nion )!-/!9nion )!-/! :ea )!-/!:ea )!-/!

:arsley ),!:arsley ),!

:epper )2-2!!:epper )2-2!!

:otato )!-/!:otato )!-/!

%hubarb )!%hubarb )!

%ice !%ice !

Spinach !-!Spinach !-!


7/73

:ercentage lost at& 2!>&=ood 7>& 2!>&

Beans // /Beans // /

&auliflo4er . 26&auliflo4er . 26

Lettuce /6 72Lettuce /6 72:arsley )/ ,!:arsley )/ ,!

:eas )! /6:eas )! /6

Spinach /2 .!Spinach /2 .!

Spinach '4inter( , 22Spinach '4inter( , 22


8/73

#ll $lants can synthesi%e &itamin

'ost animals can synthesi%e vitamin except umans, *uinea pigs, red+

vented ulbul, fruit eating bat, rainbo!trout, oho salmon

-hey lack L+gulono++lactone oxidase


9/73

/+0+glucose

glucose+1+phosphate

uridine diphosphate glucose

uridine diphosphate glucuronic acid

0+glucuronic acid++phosphate

0+glucuronic acid 3#0$45

L+gulonate pentosephosphate

3#0$ path!ay

L+gulono++lactone O2 2O2 L+gulono++lactone oxidase 2+keto+L+gulonolactone

spontaneous isomeri%ation

L+ascorbic acid


10/73

Synthetic rate 3Synthetic rate 3?? 3urno#er 3urno#er Species 'mg@kg body 4eight( 'days( '"day(Species 'mg@kg body 4eight( 'days( '"day(

Mouse )2 )$7 !Mouse )2 )$7 !

olden hamster 2! 2$, 26olden hamster 2! 2$, 26

%at 2 2$6 26%at 2 2$6 26

%abbit /$ ).%abbit /$ ).

uinea pig ! /$. ).uinea pig ! /$. ).

8uman ! )!-2! /8uman ! )!-2! /


11/73

Occurs primarily by active transport 6aturable and dose dependent

6imple di7usion and carrier+mediated

contribute to small extent $rior to absorption, ascorbic acid may

be oxidi%ed to dehydroascorbate 8ithin enterocytes, dehydroascorbate

reduced to ascorbic acid 0ehydroascorbate reductase

9e:uires reduced *6


12/73

Occurs primarily in distal portion of 6;

< absorbed decreases !ith increased vitaminintake.

1< at high intakes (1 g) and =>< at lo!intakes (? 2@mg)

Over range of 2@ to 2 mgAd, get >@+=B<absorption

$otential Factors ;mpairing #bsorption

$ectin (C.2 gAd)

Dinc (=.E mgAd)

igh iron content in *; can lead to destructionof ##


13/73

2@@mgAday is a particularupper limit give 2mgAL

plasma level 2,B@@mgAday increase plasma

level to BmgAL

#ctively absorbed =>< eciency at 2@mgAday 1< eciency at G2gAday


14/73

#bsorption #ctive transportsystem, 3a and #-$ dependent. Hciency of absorption decline !ith

dose above g.

-ransport in plasma as ascorbic acid uman cells become saturated at

@@mgAday.

ellular uptake by #ctive transportsystem, 3a and #-$ dependent. Iptake glucose inhibits, insulin

stimulates


15/73

-ransport across basolateral membrane

6odium+independent carrier+mediatedtransport

-ransported in plasma in free form

#lbumin may also transport someascorbate and dehydroascorbate (B<seen in circulation)

#scorbate moves freely into cells

oncentration of ascorbate ho!everis much higher in some tissues

#drenal gland, pituitary gland and eye

'ay be actively transported into these tissues


16/73

0ehydroascorbic acid -aken up by red blood cells, lymphocytes

and neutrophils

9educed to ascorbic acid !ithin cells

-issue and plasma level reJect intakeuntil intake exceeds G=@mgAday.


17/73

;n vital organs !ith active metabolism

-otal body pool si%e about B@@mg

alf life about 2@ days

-urnover rate mgAkgAday

0aily utili%ation breakdo!n is @.2mgAkg

fat free !eight


18/73

3issue itamin & 'mg@)!!g 4et tissue(3issue itamin & 'mg@)!!g 4et tissue(

:ituitary gland 7!-!:ituitary gland 7!-! Adrenal glands /!-7! Adrenal glands /!-7!

ye lens 2-/)ye lens 2-/)

Brain )/-)Brain )/-)

Li#er )!-)6Li#er )!-)6

Spleen )!-)Spleen )!-);idneys -);idneys -)

8eart muscle -)8eart muscle -)

Lungs ,Lungs ,

Skeletal muscle /Skeletal muscle /

3estes /3estes /

3hyroid 23hyroid 2

Leucocytes /Leucocytes /

:lasma !$7-)$!:lasma !$7-)$!

Source< Adapted from Basu and Schorah ').2(Source< Adapted from Basu and Schorah ').2(


19/73

Occurs primarily in liver &itamin is oxidi%ed (removal of 2

electrons and 2 protons) todehydroascorbate Follo!s the formation of

semidehydroascorbate radical. Oxidi%ed form may be reduced back to

ascorbate by *6, 3#0 or 3#0$. Oxidi%ed form may be further oxidi%ed

to 2,E+diketogulonic acid. 0iketolulonic acid is cleaved into oxalic

acid and C or B carbon sugars.


20/73

Oxidation ascorbic acid, mono+dehydro+

ascorbic acid, dehydro+ascorbic acid.

Hxcretion 2@+2B < ascorbic acid and 0##,2@< diketogulonic acid, C@+CB< oxalate

0ehydroascorbate, diketoglulonate, oxalicacid and excess ascorbate excreted in urine 2B< of vitamin intake is excreted as oxalic acid

#mount of &itamin Kltered and then reabsorbedby kidneys depends on plasma vitamin

concentrations $lasma levels above .C mgAdL exceeds renal

threshold and vitamin !ill not be reabsorbed.


21/73

+2 #scorbic acid 0ehydroascorbic acid

52

52O

#scorbate+2+sulphate 0iketogulonic acid

+@2

5 2O Lyxonicacid

5O

5 2O

Oxalic acid 5 -hreonic acid +@2

+O2 5 2O

52 ylonic aci

ylose

6ource asu and 6chorah,=>2.


22/73

Hxcretion reduced !hen intake islo!

Irinary excretion ody pool ?,B@@mg leads toonly metabolites in urine

ody pool MB@@mg leads toproportionately more ascorbatein the urine (can mask clinicaltests)


23/73

&itamin increases intestinalabsorption of nonheme iron 9educes FeE5 to Fe 25 or forms a

soluble complex !ith the iron Hxcessive iron in presence of

vitamin can accelerate theoxidative catabolism of vitamin

&itamin aids incorporation of ironinto ferritin


24/73

&itamin may increase absorption andexcretion of heavy metals Form chelates !ith metals

&itamin intakes above 1@@ mgAd mayinterfere !ith copper metabolism

&itamin helps keep folate in its

reduced and active form.


25/73

Hlectron transport #ntioxidant functions $rooxidant properties Hn%yme cosubstrate functions

ollagen synthesis 3eurotransmitter metabolism

arnitine synthesis 0rug and steroid metabolism -yrosine metabolism


26/73

'etal ion metabolism

#ntihistamine reactions

ealth e7ects ;mmune function

8ound healing

ardiovascular disease

0iabetes, cataracts

$ulmonary function, ancer


27/73

#ntioxidant and $ro+oxidant #ctivity 9educing agent (antioxidant) (#+)

0onate electrons and hydrogen ions

#+ may react !ith free radicals and reactiveoxygen species

9eactive oxygen species O (hydroxy radical), O2+ (superoxide radical),

2O2 (hydrogen peroxide), and O2 (hydroperoxyl radical) #ttack phospholipids and protein embedded in

membranes Oxidi%e L0L and red blood cells


28/73

Ascorbate (AH-) + OH.

semidehydroascorbate radical (A-) + H2O

AH- + O2- + H+A- + H2O2

AH- + H2O2 A- + H2O


29/73

2 semidehydroascorbate radicals

ascorbate + dehydroascorbate

2 semidehydroascorbate radicals (A-) + 2GSH

2 ascorbate (AH-) + GSSG

Dehydroascorbate (A) + 2 GSHascorbate (AH-) + GSSG

2 semidehydroascorbate (A-) + NADH + H+

2 ascorbate (AH-) + NAD+


30/73

ascorbate NO oxidase N2@

#scorbic acid

0ehydroascorbic acid

*66* glutathione 2 *6

dehydrogenase


31/73

Ascorbate (AH-) + Fe+3 or C+2

semideydroascorbate radical (A-) + Fe+2 or C+!

"he #rodcts Fe+2 a$d C+! ca$ #roceed to case cell dama%e

%e$eratio$ o& reacti'e oy%e$ s#ecies a$d &ree radicals.

Fe+2

or C+!

+ H2O2Fe+3 or C+2 +OH- + OH

.

Fe+2 or C+! + O2Fe+3 or C+2 + O

2

-


32/73

'ost abundant protein found in body 'aPor component of most connective

tissue 6kin, bone, cartilage, tendons, ligaments #ll collagen (nG=) have a triple helical

structure For the collagen molecule to aggregate into its

triple+helix conKguration selected prolineresidues must be hydroxylated forminghydroxyproline 9e:uires di+oxygenase en%ymes, alpha Q*,

reduced iron (Fe52), ascorbate #scorbate functions to reduce iron (cofactor)

back to its ferrous state.


33/73

O C

CH

Proline

CH2

CH2

HCCH2

N

HN

NH2(CH2)4

Lysine

(CH2)2

COOHCO2

α-ketogutarate

O C

COOH

OC (CH2)2

COOH

COO*H

Succinate

O C

CH

Hydroxyproline

CH

CH2

HCCH2

N

HN

(CH2)4

HydroxylysineO C

OH

CH2 NH2CH

e!ydro-ascor"ate

#e$%O2

&scor"ate

#e$2

&scor"ate unctionsin t!e !ydroxylationo peptide-"oundproline and lysine in

*OH


34/73

&itamin also re:uired forhydroxylation of lysine residues

ydroxylysyl residues permit cross+

linking or collagen and other post+translational modiKcations

&itamin may also inJuence m93#

levels needed for collagen synthesis.


35/73

&itamin re:uired for 2 reactions inthe synthesis of carnitine fromtrimethyllysine

-rimethyllysine conversion to E hydroxy+trimethyllysine re:uires -rimethylhydroxylase (dioxygenase), alpha Q*,

Fe52 and ascorbate

C+butyrobetaine to carnitine re:uires C+butyrobetaine hydroxlyase (dioxygenase),

alpha Q*, Fe52 and ascorbate


36/73

(CH2)2

COOHCO2

α-ketogutarate

COOH

OC (CH2)2

COOH

COOH

Succinate

e!ydro-ascor"ate

#e$%O2

&scor"ate

#e$2ri+et!yl

lysine!ydroxylase

CH2CH2

CH2

CH2

H%C CH%

CH%

$NH%COO-

$N

CH

ri+et!yl lysine

CH2CH2

CH2

HC , OH

H%C CH%

CH%

$NH%

COO-

$N

CH

%-OH-ri+et!yllysine

The function of vitamin C in carnitine

CH CH%


37/73

CH

2CH2

CH2

HC , OH

H%C CH%

CH%

$N

%-OH-ri+et!yllysine

$NH%

COO-

CH

4-"utyro"etaine

alde!yde

lycine

$NH%

COO-

CH2

CH

2CH2

CH2

HC

H%C CH%

%

$N

O

N&$

N&H4-"utyro"etaine

α-ketogutarate

Succinate

CO2

e!ydro-ascor"ate

#e$%O2

&scor"ate

#e$24-"utyro"etaine

!ydroxylase

CH

2HC , OH

CH2

COO-

H%C CH%

CH%

$

N

Carnitine

Serine !ydroxy+et!yltranserase-PLP-dependent

The function of vitamin C incarnitine


38/73

Lysine 6-N-Trimethyl lysine

1+3+-rimethyllysine ydroxylase

3-Hydroxy-6-N-Trimethyl lysine

*lycine

γ-Butyrobetaine Carnitine

+utyrobetaine ydroxylase

Carnitine


39/73

ydroxylation of $henylalanine 9e:uires phenylalanine mono+oxygenase

(hydroxylase), Fe52, O2,

tetrahydrobiopterin, 3#0$, vitamin reducing po!er is supplied ultimately by

3#0$ but immediately by tetrahydropterin

&itamin may function in regeneration of

tetrahydrobiopterin from dihydrobiopterin.

$NH%$NH%


40/73

CH2 , CH , COO-

CH2 , CH , COO-

$NH%

CH2

O

CH2 , CH , COO

$NH%

HO

O2 H2O

etra!ydro-"iopterin

i!ydro-"iopterin

N&(P)$ N&(P)H

*

P!enylalanine !ydroxylase #e2$

COO-C

HO

H 2 O

O

2

i ! y

d r o -

" i o p

t e r i n

* e t r a

! y d r o -

" i o p r

e t i n

N & (

P ) H

N & (

P ) $ * y

r o s i n e

+ o n o - o

x y g e

n a s e

. ! y d r

o x y l a

s e - # e 2 $

P!enylalanine yrosine

α-keto-glutara

gluta+a

rana+inas

-/ita+in 01-dependent

HO

HO %4-di!ydroxyp!enylalanine(OP&) P-!ydroxyp!enylpyru/at

The role of vitamin C* in thephenylalanineand tyrosinemetabolism,includingnorepinephrinesynthesis

$NH%CO2


41/73

CH2 , CH , COO-HO

HO

4-di!ydroxyp!enylalanine(OP&)

CO2

OP&decar"oxylase , 3ita+in 01(CH2)2 , NH2HO

HO

opa+ine

O2

H2O Cu2$

Cu$

opa+ine+ono-oxygenase

e!ydro-ascor"ate

&scor"ate

CH , CH2 , NH2HO

HOOH

Norepinep!rine

The role of vitamin C*in the phenylalanineand tyrosinemetabolism, includingnorepinephrinesynthesis


42/73

O2 CO2

Cu2$ Cu$

P-!ydroxy-

p!enylpyru/ate!ydroxylase

e!ydro-ascor"ate

CH2

O

COO-C

HO

P-!ydroxyp!enylpyru/ate

&scor"ate*

OH

CH2 , COO

HO

Ho+ogentisate

O2

Cu2$

Cu$

P-!ydroxy-p!enylpyru/ate!ydroxylase

e!ydro-ascor"ate

&scor"ate

-OOC , CH 5 CH , C , CH2 , C , CH2 ,

OO

4-+aleylacetoacetate

The role of vitamin

C* in thephenylalanine andtyrosinemetabolism,includingnorepinephrinesynthesis


43/73

"yrosi$e

#-Hydroy#he$yl#yr'ic acid

Homo%e$tisic Acid

*aleylacetoacetic Acid

Fmarylacetoacetic Acid

Acetoacetic Acid

Acetoacetyl CoA

#-hydroy#e$yl#yr'ate dioy%e$ase

Homo%e$tisate dioy%e$ase

Ascorbate C2+

Ascorbate Fe2+


44/73

"yrosi$e

3,-dihydroy#he$ylala$i$e

(Do#a)

Do#ami$e

Nore#i$e#hri$e

C!+

itami$ C

Do#ami$e

*o$o-oy%e$ase


45/73

$eptidylglycine amidating oxygenase 9e:uires u5, ascorbate, O2 Functions to cleave the carboxyl+

terminal through use of molecular O2. #mino group is retained as terminal amide

!hile rest is released as glyoxylate

'any of amidated peptides resulting from

this reaction are active as hormones,hormone+releasing factors andneurotransmitters

H.g.*astrin, Q, oxytocin, corticotropin,calcitonin, thyrotropin, vasopressin


46/73

$roline O+$roline 0opamine 3orepinephri

$roline 0opamine

'onooxygenase 'onooxygenase

6emihydroascorbate #scorbate 6emidehydroascorbate #scor

#scorbate 6emihydrosascorbate

O #midating O O

(;nactive ormone)9++3+2OO Hn%yme 9++32 5+OO (#midated or

=e2C =e/C &uC &u2C


47/73

6erotonin can be synthesi%ed fromtryptophan

ydroxylation of -ryptophan to B+

hydro-rp 9e:uires tryptophan mono+oxygenase

O2, tetrahydrobiopterin, vitamin and 3#0$

0ecarboxylation of B+O-rp to6erotonin


48/73

-ryptophan mono+oxygenase+Fe25

O2 2@

O2

-etrahydrobiopterin 0ihydrobiopterin

(B+hydroxytryptamine)

R

3#0$5 3#0$55

R&itamin may function in tetrahydrobiopterin regeneration

3ryptophan3ryptophan -hydroxytryptophan-hydroxytryptophan

Serotonin


49/73

Reaction Substrate Enzyme Product

!

2

3

,

/

p-OH-#he$yl#yr'atehydroylase!

0e#tidyl 1-#roli$e

0e#tidyl 1-#roli$e

0e#tidyl 1-lysi$e

/- N -"rimethyl 1-lysi$e

,- N -"rimethylami$obtyrate

p-OH-#he$yl#yr'ate

0rolyl ,-hydroylase2

0rolyl 3-hydroylase2

1ysyl hydroylase2

/- N -"rimethyl 1-lysi$ehydroylase2

,- N -"rimethyl ami$o-btyratehydroylase2

Homo%e$tisate

0e#tidyl ,- tra$shydroyl-1- #roli$e0e#tidyl 3- tra$shydroyl-1- #roli$e0e#tidyl-erythrohydroy- 1-

lysi$e

rythro-3-hydroy-/- N -trimethyl 1-lysi$e

3-Hydroy-,- N -trimethyl ami$o-btyrate

! 4-5eto%ltarate is $ot re6ired as a cosbstrate.2 4-5eto%ltarate is re6ired as a cosbstrate

Source7 modi&ied &rom $%lard a$d Sei&ter (!89/)


50/73

&itamin and -he ommon old g &it Ad S B@mgAd

3umber of colds, severity and duration

g &it Ad decreases duration andseverity of symptoms

&itamin and ancer ontroversial

Hpidemiologic studies suggest inverserelationship bet!een &itamin andcancers of oral cavity, esophagus, anduterine cervix


51/73

linical 6tudies 6ome researchers have sho!n that

survival time in cancer patients may beprolongedT

Others have not sho!n this

$ossible $rotective 'echanisms #bility to act as a reducing agent

0etoxify carcinogens &itamin ingested !ith nitrates or nitrites

can prevent formation of nitrosamines ornitrosamides


52/73

#therosclerosis 3egative relation !ith vitamin

L0L lipid peroxidation

ataracts 3egative relation !ith vitamin

one density $ositive relation !ith vitamin

8ound healing and connectivetissue metabolism


53/73

=>= 90# is 1@ mg for adults ased on maintenance of body pool of

B@@mg

Level represents the amount of the vitaminthat could be held !ithin the body tissuesand Juids !ithout loss via kidneys.

=>= 90# is @@ mg for smokers ;ncreased metabolic turnover of vitamin

!as seen in smokers.


54/73

2@@@ 09; 90# ased on near maximal neutrophil

concentration

#dult male =@ mg #dult female UB mg 6mokers extra EB mg

IL #dult 2@@@ mg Osmotic diarrhea


55/73

FemalesFemales MalesMales

Life stage groupLife stage group RDARDA

mg!d"mg!d"RDARDA

mg!d"!mg!d"!# L$$# L$$

mg!d"mg!d"

%nfants%nfants

&' ( mont)s&' ( mont)s *&$*&$ *&$*&$ +D+D

,'- mont)s,'- mont)s /&$/&$ /&$/&$ +D+D

C)ildrenC)ildren

-' 0 yrs.-' 0 yrs. -/-/ -/-/ *&&*&&

*' 1 yrs.*' 1 yrs. // // (/&(/&

2'-0 yrs.2'-0 yrs. */*/ */*/ -&&-&&

-*'-1 yrs.-*'-1 yrs. (/(/ ,/,/ -1&&-1&&3-2 yrs.3-2 yrs. ,/,/ 2&2& &&&&&&

Pregnancy ! lactation.Pregnancy ! lactation.

4 -1 yrs.4 -1 yrs. 1& ! --/1& ! --/ '' -1&&-1&&

-2'/& yrs.-2'/& yrs. 1/ ! -&1/ ! -& '' &&&&&&

From institute of Medicine, Food and utrition board! "ietar# $eference %nta&es for 'itamin C, 'itamin , elenium and carotenoids! *as+ington,

"C ational Academ# -ress .000!


56/73

RDA5RDA5 CriterionCriterion

:-/ mo:-/ mo A'era%e hma$ mil; co$te$tA'era%e hma$ mil; co$te$t

?

!8-: y!8-: y Near-maimal $etro#hil co$ce$tratio$ a$d a$tioida$t Near-maimal $etro#hil co$ce$tratio$ a$d a$tioida$t #rotectio$ #rotectio$

@! y@! y Near maimal $etro#hil co$ce$tratio$ a$d a$tioida$t Near maimal $etro#hil co$ce$tratio$ a$d a$tioida$t

#rotectio$ #rotectio$

0re%$a$c0re%$a$cyy

A &or $o$#re%$a$t adolesce$t %irls or =ome$ a$dA &or $o$#re%$a$t adolesce$t %irls or =ome$ a$dtra$s&er to the &ets a$d hemodiltio$.tra$s&er to the &ets a$d hemodiltio$.

1actatio$1actatio$ A &or $o$#re%$a$t adolesce$t %irls or =ome$ a$d lossesA &or $o$#re%$a$t adolesce$t %irls or =ome$ a$d losses

i$ hma$ mil;i$ hma$ mil;

#L5#L5 2:::m%Bd based o$ osmotic diarrhea a$d G distrba$ces2:::m%Bd based o$ osmotic diarrhea a$d G distrba$ces


57/73

&itamin intakes ? @ mgAd resultin scurvy 6ee !hen total body pool is ? E@@ mg

6ymptoms bleeding gums, small skin discoloration

due to ruptured blood vessels, easybruising, impaired !ound and fracturehealing, Point pain, loose and decaying

teeth, hyperketatosis of hair follicles. 6curvy rare in I6

Lo! plasma vitamin levels observedin elderly


58/73

Corkscrew air


59/73

!erifollicular !etechiae


60/73

"curvy


61/73

um changes in infant

scur#y<

3he s4elling and

hemorrhages are confined to

the areas of the gum

surrounding the erupting

teeth$


62/73

ums in scur#y<

3he gums are blue-red and glossy

s4ollen in this patient 4ith se#ere

scur#y$ 3he earliest changes ares4elling of the internal dental

papillae and tendency to bleed

easily$ Lesions occur only in

relation to teeth and so in young

infants and edentulous adults they

are absent$ 1n ad#anced cases

there is usually an element of

infection and antibiotics as 4ell as

#itamin & are reDuired for healing


63/73

ery ad#anced gum lesions in scur#y


64/73

9rbital hemorrhage<

3his is a dramatic but infreDuent

sign of scur#y$ 3here is complete

clearing 4ith treatment$


65/73

Splinter hemorrhage<

1n this unusual sign in scur#y the

hemorrhages are arranged in a

semicircular lattice in#ol#ing nail

beds$ 3hey are more extensi#e

than those in sub-acute bacterialendocarditis$


66/73

:erifillicular petechiae<

Minimal bleeding into the hair follicles is

pathognomonic of #itamin & deficiency

and is often the earliest clinical

manifestation$ 1n #itamin ; deficiency*

thrombocytopenia and other conditions*

petechiae are situated in areas of skin

unrelated to the hair follicles$ 1n

perifillicular hyperkeratosis* there is no

bleeding and hyperkeratosis is present$cchymoses de#elop in more ad#anced

deficiency and are the most freDuent sign

in E4orkhouseF scur#y in old men$ Wound

healing is markedly delayed$


67/73

0lasma ascorbic >&&y coat ascorbic >ody #ool o& acid acid i$ lecocytes(?C) ascorbic acidDay (m% l-!) (mol l-!) (% !:-9 ) ($mol !:-9 ) (%) ($mol) Cli$ical state

: 9-! ,-9 2!-< !!8-323 :./-!. 3.,-9.2: 3 !< !:-39


68/73

#fter CB+>@ days of stopping vitamin intake

-he Cs emorrhagic signs yperkeratosis of hair follicles

ypochondriasis ($sychological)

ematological (impaired iron absorption)


69/73

-oxicity more likely !ith ingestion ofseveral large (g) doses than onesingle dose 9emember absorption is saturable and

dose dependent Qidney stonesV

oxalic acid 5 calcium make up kidneystones

$eople predisposed to kidney stones should avoidhigh intakes

Irate crystals and urate kidney stones &itamin competes !ith uric acid

reabsorption


70/73

-oxicity is rare ;ncreased intake and 1 and 2

utili%ation hronic high doses of vitamin

may be unsafe for those unable toregulate absorption of iron emochromatosis

'ay interfere !ith clinical tests -ests for glucose in urine

0ecrease intake gradually to avoidscurvy+like symptoms


71/73

lood, serum or plasma levelsmost commonly used.

hange in response to recent

dietary &itamin intakes $lasma or serum levels most

sensitive indicators of deKciency

8hite blood cell content reJectsbody stores 'easurement is technically dicult.


72/73

itami$ C %ro# 0lacebo %ro#

itami$ C Dratio$

Stdy (%Bday) (mo$ths) n ColdsB#erso$Byear n ColdsB#erso$Byear (8C)

! ! 3 ,:< . ,!! .8 :.83(:.93-!.:,)

2 ! 3 338 /.< 3,8


73/73

itami$ C CasesBtotal sbIectsStdy $&ectio$ (%Bday) itami$ C 0lacebo O(8 C)

Studies of infection incidence!a He#atitis 3.2 /B8: 9B9 :./8(:.2/-!.9:)2a 0$emo$ia 2 !B33!

met vitamin c 4 april

Documents