Ascorbic Acid - American Chemical Society

18 Nutritional and Health Aspects of

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Ascorbic A c i d M Y R O N BRIN Department of Clinical Nutrition, Hoffmann-La Roche Incorporated, Nutley, NJ 07110

Ascorbic acid (AA) is not synthesized by humans, making it an essential dietary vitamin for this species. Although clini cal deficiency (scurvy) is rare, marginal inadequacy results in behavioral changes, reduced drug metabolism, and reduced immunocompetence, thereby affecting social and work functions. AA is important in increasing iron absorption, in collagen synthesis, and as a biological blocking agent against nitrosamine formation; AA has also been used experimentally to reduce incidence of bladder tumors in mice. Heavy smoking increases the risk group fourfold. Blood levels are reduced in myocardial infarction and other conditions involving physical, infective, or traumatic insult. Scurvy still persists in certain parts of the world. The appropriate intake levels of vitamin C for each of its physio logical functions have not yet been fully defined.

Humans require ascorbic acid as a vitamin. A recent report (1) established that the genetic basis of this need is a lack of L-gulonolactone dehydrogenase, the last enzyme in the synthetic sequence. This vitamin's function in, for example, preventing scurvy, and facilitating tyrosine and proline metabolism, is well documented and accepted. Virtually all other aspects of the health applications of vitamin C are controversial, including establishing a definitive daily requirement, which has varied over the years both within and between countries. Perhaps it is more than happenstance that vitamin C is separated by name from the other water soluble "B" vitamins. Historically, this sepa ration was the result of the normal procedure of labeling unknown dietary factors, as C was differentiated from B—which later was shown to be a complex group rather than an individual, water-soluble vitamin. It was 0065-2393/82/0200-0369$06.00/0 © 1982 American Chemical Society Seib and Tolbert; Ascorbic Acid: Chemistry, Metabolism, and Uses Advances in Chemistry; American Chemical Society: Washington, DC, 1982.

370

ASCORBIC

d i s c o v e r e d t h a t the B - v i t a m i n g r o u p c o m p r i s e d a series of

ACID

compounds,

f o r w h i c h e a c h i n d i v i d u a l c o m p o u n d c o u l d b e a s s i g n e d a h i g h l y specific v i t a m i n - c o e n z y m e s t r u c t u r e , a n d w h i c h f a c i l i t a t e d v e r y specific

enzyme

reactions. S u c h was not the case for w a t e r - s o l u b l e v i t a m i n C , f o r w h i c h a c o e n z y m e s t r u c t u r e has n o t yet b e e n i d e n t i f i e d . T h e i d e n t i f i c a t i o n of t h e c o e n z y m e forms of the B v i t a m i n s has l e n t c r e d i b i l i t y to t h e i r essen t i a l i t y i n h u m a n n u t r i t i o n . So, w a t e r - s o l u b l e v i t a m i n C m u s t b e e v a l u a t e d


at a n o t h e r l e v e l .

T h a t l e v e l is p h y s i o l o g i c a l f u n c t i o n , r a t h e r t h a n b y

specific reactions. O n e c o u l d m o r e r e a d i l y e x p l a i n the c l i n i c a l signs of s c u r v y o n the basis of the f u n c t i o n of v i t a m i n C i n c o l l a g e n f o r m a t i o n , t h a n one c o u l d e x p l a i n the d e v e l o p m e n t of w e t b e r i b e r i for t h i a m i n e , or of cheilosis for r i b o f l a v i n f u n c t i o n . F o r instance, w h y s h o u l d n ' t r i b o f l a v i n cause b e r i b e r i , a n d t h i a m i n e cause c h e i l o s i s — r a t h e r t h a n the reverse? W e cannot e x p l a i n this. T h e s i t u a t i o n exemplifies t h a t w e often c a n n o t e x p l a i n the c l i n i c a l findings

o n the basis of w h a t is k n o w n a b o u t t h e b i o c h e m i c a l f u n c t i o n

of the v i t a m i n .

T h e r e is s t i l l m u c h m o r e to b e l e a r n e d a b o u t v i t a m i n

n u t r i t i o n , a n d this is e x e m p l i f i e d b y v i t a m i n C .

Bioactivity T h e r e l a t i v e b i o p o t e n c y of s y n t h e t i c vs. n a t u r a l v i t a m i n C is o p e n to conjecture.

B y a d m i n i s t e r i n g orange juice vs. s y n t h e t i c v i t a m i n C

a d u l t males, a n d m e a s u r i n g levels of the v i t a m i n i n s e r u m ,

to

leucocytes,

a n d u r i n e , the s y n t h e t i c v i t a m i n was b u t s l i g h t l y m o r e b i o a v a i l a b l e

(2).

U s i n g a n i n t r a l u m i n a l i n f u s i o n t e c h n i q u e of y o u n g m a l e a d u l t s n o d i f ferences i n b i o a v a i l a b i l i t y w e r e f o u n d

(3).

P r e s u m a b l y , the s y n t h e t i c

L-ascorbic a c i d is e q u a l l y b i o a v a i l a b l e to t h a t f o u n d i n n a t u r e .

Immunocompetence V e r y p r o v o c a t i v e i m m u n o l o g i c a l w o r k has b e e n d o n e w i t h v i t a m i n C d u r i n g the last d e c a d e . W h i t e b l o o d c e l l levels of v i t a m i n C h a v e b e e n m e a s u r e d to e v a l u a t e n u t r i t i o n a l status for this n u t r i e n t for a l m o s t f o r t y y e a r s ; therefore, i t is not s u r p r i s i n g t h a t r e l a t i o n s h i p s to tence h a v e e m e r g e d .

I n c u b a t i o n of leucocytes

immunocompe

w i t h ascorbic

a c i d at

p h y s i o l o g i c a l p H augments the r a n d o m m i g r a t i o n a n d chemotaxis o n e f o l d to t h r e e f o l d w i t h o u t affecting p h a g o c y t i c c a p a c i t y (4). w e l l as s t i m u l a t i o n of hexose m o n o p h o s p h a t e

from

T h i s , as

s h u n t a c t i v i t y , w a s dose

r e l a t e d , a n d c o u l d be r e v e r s e d b y w a s h i n g the cells. T h e effect o c c u r r e d at p h y s i o l o g i c a l concentrations of t h e v i t a m i n .

G l u t a t h i o n e also s t i m u

l a t e d the s h u n t a n d the m i g r a t i o n . T h i s finding w a s c o n s i d e r e d cant because i n polymorphonuclear lymphocytes

(PMN),

is a c c o m p a n i e d b y i n c r e a s e d o x y g e n c o n s u m p t i o n , hexose

signifi

phagocytosis

monophosphate

Seib and Tolbert; Ascorbic Acid: Chemistry, Metabolism, and Uses Advances in Chemistry; American Chemical Society: Washington, DC, 1982.

18.

Ascorbic Acid: Nutrition ir Health

BRIN

371

shunt activity, a n d hydrogen peroxide production ( 5 ) . V i t a m i n C de ficient g u i n e a p i g s y i e l d e d f e w e r m a c r o p h a g e s ( f r o m p e r i t o n e a l e x u d a t e ) , w i t h r e d u c e d m i g r a t i o n , b u t d i d n o t affect phagocytosis

Thein

(6).

v i t r o a d d i t i o n of v i t a m i n C p a r t i a l l y r e v e r s e d t h e r e d u c e d m i g r a t i o n . I n the g u i n e a p i g , a s c o r b i c a c i d d e p l e t i o n r e s u l t e d i n depressed i m m u n o l o g i c a l response ( 7 ) , a n d h i g h v i t a m i n dosage s u p p o r t e d elevated m i t o t i c a c t i v i t y ( 8 ) . P M N c o n t a i n h i g h levels of ascorbate ( 9 ) ; these levels are


m a r k e d l y r e d u c e d f o l l o w i n g v i r a l i n f e c t i o n (10,11),

a n d revert t o w a r d

n o r m a l after r e c o v e r y ( I I ) . L e v e l s are also r e d u c e d i n other l e u k e m i c and hematological conditions

(12).

Also, using the plaque

inhibition

m e t h o d u t i l i z i n g v e s i c u l a r stomatitis v i r u s , i n c r e a s e d s e r u m i n t e r f e r o n f o l l o w i n g t h e subcutaneous

i n j e c t i o n of either a s c o r b i c

s a l i c y l a t e , o r caffeine i n m i c e w a s d e m o n s t r a t e d (13).

acid, sodium

Similar

findings

of i n c r e a s e d i n t e r f e r o n i n d u c t i o n w e r e o b s e r v e d f o l l o w i n g exposure of h u m a n e m b r y o s k i n i n t h e presence of a s c o r b i c a c i d to either N e w c a s t l e v i r u s or p o l y I / p o l y

C (14).

A l s o , a t h r e e f o l d i n t e r f e r o n increase i n

m o u s e cultures f o l l o w i n g p o l y I / p o l y C a d d i t i o n to m o u s e c e l l cultures c o n t a i n i n g v i t a m i n C , a n d also i n m i c e i n v i v o g i v e n 250 m g % ascorbic a c i d i n d r i n k i n g w a t e r , w h e n exposed observed

(13).

to m u r i n e l e u k e m i a v i r u s w a s

A d o u b l i n g of D N A synthesis b y T - l y m p h o c y t e s w a s

r e m a r k e d i n spleens of m i c e o n a h i g h ascorbate d i e t f o l l o w i n g c o n c o n a v a l i n A ( c o n A ) ( 1 5 ) . I n h u m a n s , t h e c o n s u m p t i o n of 1 g of ascorbic a c i d / d f o r 75 d r e s u l t e d i n i n c r e a s e d s e r u m levels of I g A , I g M , a n d C - 3 c o m p l e m e n t (16).

I n c r e a s i n g t h e w e e k l y i n t a k e b y h u m a n volunteers to

2 and 3 g / d enhanced neutrophil motility and lymphocyte transformation to p h y t o h e m a g g l u t i n i n a n d c o n A (17,18).

I n one s t u d y , h o w e v e r , hexose

m o n o p h o s p h a t e s h u n t a c t i v i t y a n d s e r u m levels of I g A , I g G , I g M , C ' 3 , a n d C'4,

1

a n d total complement

a c t i v i t y w e r e n o t affected

(18).

Also, the

n u m b e r s of l e u k e m i c cells i n c u l t u r e w e r e r e d u c e d b y 0.3 m M a s c o r b i c a c i d (19).

N o r m a l m y e l o i d cells w e r e unaffected, a n d g l u t a t h i o n e w a s

ineffective.

I n s u m m a r y , a s c o r b i c a c i d p r o b a b l y influences v a r i o u s p a

rameters of i m m u n o c o m p e t e n c e ,

a n d attention should be directed to

s t u d y i n g effects of s u p p l e m e n t a t i o n o n these p h e n o m e n a i n t h e e l d e r l y , subjects o n i m m u n o s u p p r e s s i v e d r u g s , p r e g n a n t w o m e n (20), a n d other risk groups.

Cancer T h e relationship between

a s c o r b i c a c i d a n d c a n c e r is of g e n e r a l

interest. O n e of the first studies i n this d i r e c t i o n (21) d e m o n s t r a t e d that v i t a m i n C g i v e n to m i c e p r e v e n t e d t h e c a r c i n o g e n i c i t y i n u r i n a r y b l a d d e r s of i m p l a n t e d 3 - h y d r o x y a n t h r a n i l i c a c i d . A f e w years later t h e a b i l i t y of 1

These factors are body proteins associated with immunocompetence.


1

372

ASCORBIC

ACID

ascorbate t o b l o c k n i t r o s a m i n e f o r m a t i o n w a s d e m o n s t r a t e d ( 2 2 ) u s i n g rat h e p a t o t o x i c i t y as a m o d e l .

T h e ascorbate-nitrosamine relationship

has b e e n a d d r e s s e d i n c h a p t e r 24 i n this b o o k .

M o r e recently, P a u l i n g

a n d c o w o r k e r s h a v e s t u d i e d t h e usefulness of a s c o r b i c a c i d i n i m p r o v i n g the q u a l i t y of a n d l e n g t h e n i n g t h e l i f e of c a n c e r p a t i e n t s ( 2 3 ) , a n d i n o b t a i n i n g r e m i s s i o n of r e t i c u l u m c e l l s a r c o m a ( 2 4 ) . A t t e m p t s t o c o n f i r m these findings b y others ( 2 5 ) h a v e b e e n u n s u c c e s s f u l , a l t h o u g h different


e x p e r i m e n t a l designs, s u c h as p r i o r s u p p r e s s i o n of t h e i m m u n e system, w e r e u s e d ( 2 6 ) . C u r r e n t i n v i t r o studies i n c o n j u n c t i o n w i t h c h e m o therapy i n neuroblastoma (27) a n d i n malignant melanoma (28) dem onstrated c e l l r e v e r s i o n to n o r m a l b y v i t a m i n C . T h e m e c h a n i s m of a c t i o n m a y b e m e d i a t e d t h r o u g h t h e e n h a n c e d p r o d u c t i o n of h y d r o g e n p e r o x i d e i n t u m o r cells l o w i n catalase a n d / o r p e r o x i d a s e .

This mech

a n i s m m a y also a p p l y to t h e e n h a n c e m e n t b y a s c o r b i c a c i d of t h e t o x i c i t y of m i s o n i d a z a d o l e as a r a d i o s e n s i t i z i n g c h e m o t h e r a p e u t i c

agent i n t h e

presence of r a d i a t i o n t h e r a p y i n v i t r o ( 2 9 ) .

Red Blood Cell A s c o r b i c a c i d appears t o b e t o x i c t o c e r t a i n t u m o r tissues; h o w e v e r , it m a y increase t h e b i o l o g i c a l effectiveness of r e d b l o o d cells b y i n c r e a s i n g t h e l e v e l of 2 , 3 - d i p h o s p h o g l y c e r a t e

(30,31).

2,3-Diphosphoglycerate

is essential t o m a i n t a i n i n g t h e n o r m a l o x y g e n d i s s o c i a t i o n c u r v e of h e m o g l o b i n . T h i s increase has b e e n s h o w n i n v i t r o (30) a n d i n v i v o , i n h u m a n subjects

(31).

Micronutrient Interactions C e r t a i n i n t e r a c t i o n s of v i t a m i n C w i t h other v i t a m i n s a n d m i n e r a l s are of interest. T h e r e w a s l i t t l e effect o n e n c e p h a l o m a l a c i a i n c h i c k e n s , b u t v i t a m i n C r e d u c e d t h e i n c i d e n c e of e x u d a t i v e diathesis ( 3 2 ) p r o b a b l y because of a n i n c r e a s e d a b s o r p t i o n of s e l e n i u m . A l s o , i t w a s s u g gested t h a t a s c o r b i c a c i d m a y regenerate r e d u c e d t o c o p h e r o l f r o m t h e o x i d i z e d p h e n o x y r a d i c a l ( 3 3 ) . S c o r b u t i c m e g a l o b l a s t i c a n e m i a is asso c i a t e d w i t h t h e e x c r e t i o n of 1 0 - f o r m y l f o l i c a c i d , a n d f o l l o w i n g v i t a m i n C administration, the major metabolite was 5-methyltetrahydrofolic a c i d (34).

T h e allegation that vitamin B i

2

is d e s t r o y e d i n meals

consumed

w i t h a s c o r b i c a c i d ( 3 5 ) appears t o h a v e b e e n o v e r w h e l m i n g l y c o n t r a d i c t e d (36,37).

A n o t h e r m a j o r i n t e r a c t i o n is t h a t of a s c o r b i c a c i d w i t h

i r o n . E x c e s s i v e b o d y i r o n , s u c h as i n h e m o s i d e r o s i s , results i n a c c e l e r a t e d , a n d s o m e w h a t m o d i f i e d o x i d a t i o n of d e h y d r o a s c o r b i c

acid to carbon

d i o x i d e w i t h a r e d u c t i o n of oxalate i n u r i n e ( 3 8 ) . O n t h e other h a n d , a l t h o u g h i t has b e e n k n o w n f o r m a n y years t h a t i r o n a b s o r p t i o n is e n h a n c e d b y a s c o r b i c a c i d , i t is n o w r e c o g n i z e d t h a t greater e n h a n c e m e n t


18.

BRiN

373

Ascorbic Acid: Nutrition ir Health

is a c h i e v e d i f the a s c o r b i c a c i d a n d i r o n are present i n the g a s t r o i n t e s t i n a l tract simultaneously.

F u r t h e r m o r e , the t w o f o l d to t e n f o l d increase i n

i r o n a b s o r p t i o n at doses of 1 0 - 1 0 0 0 m g of a s c o r b i c a c i d w a s higher than anticipated (39).

somewhat

T h i s u n e x p e c t e d increase w a s one of t h e

factors t h a t s t i m u l a t e d t h e F o o d a n d N u t r i t i o n B o a r d to increase recommended


i n the 1980 e d i t i o n Some Health

the

d a i l y a l l o w a n c e ( R D A ) f o r v i t a m i n C f r o m 45 t o 60 m g , (40).

Situations

T h e usefulness of v i t a m i n C i n p r e v e n t i n g colds or a m e l i o r a t i n g t h e symptoms remains controversial. Anderson, w h o initially found reduced w i n t e r illness as a result of s u p p l e m e n t a t i o n ( 4 1 ) ,

believes

"that the

w e i g h t of the e v i d e n c e is i n f a v o r of there b e i n g s o m e effect ( a t least o n severity a n d d u r a t i o n ) f r o m s u p p l e m e n t a r y v i t a m i n C , b u t t h e m a g n i t u d e of this effect has v a r i e d w i d e l y a m o n g the different

studies."

C h a l m e r s also r e v i e w e d the " c o l d " l i t e r a t u r e a n d stated t h a t " t h e d a t a suggest t h a t a s c o r b i c a c i d does h a v e some effect o n t h e severity of c o l d s y m p t o m s , b u t t h e effects are q u a n t i t a t i v e l y so s m a l l , a n d the p o s s i b i l i t y of suggestion as the p r i m a r y m e c h a n i s m so l a r g e , t h a t i t h a r d l y seems w o r t h w h i l e for a n y o n e to take a l l these p i l l s for s u c h a l o n g time

9

(42).

I n b o t h of these studies, the a m e l i o r a t i n g effects w e r e a c k n o w l e d g e d

as

statistically significant, w i t h the j u d g m e n t that t h e y w e r e not b i o l o g i c a l l y i m p o r t a n t . Y e t c e r t a i n reports w e r e v e r y s u p p o r t i v e of the usefulness of v i t a m i n C i n colds ( 4 3 ) , just as others w e r e less so ( 4 4 ) .

T h e usefulness

of v i t a m i n C i n colds w a s r e l a t e d to a n a n t i h i s t a m i n e effect of the v i t a m i n (45)

i n g u i n e a p i g s , a n d , i n h u m a n subjects b l o o d h i s t a m i n e levels are

e l e v a t e d e x p o n e n t i a l l y w h e n p l a s m a a s c o r b i c a c i d falls b e l o w 1.0 m g a n d b e c o m e s h i g h l y significant at levels b e l o w 0.7 m g % s c o r b u t i c state is associated w i t h levels b e l o w 0.2 m g % .

(46).

%, The

O f course, t h e

p e r s o n a l t e s t i m o n i a l s of usefulness of v i t a m i n C i n colds are m a n i f o l d . T h i s is a c o m p l e x s i t u a t i o n a n d r e q u i r e s f u r t h e r s t u d y . T h e h u m a n n e e d for a s c o r b i c a c i d b o t h i n w o u n d h e a l i n g a n d i n t h e p o s t s u r g i c a l m a i n t e n a n c e of s t r o n g scar tissue is w e l l d o c u m e n t e d

(47).

T h e s e needs w e r e r e s t u d i e d m o r e r e c e n t l y i n sixty-three s u r g i c a l p a t i e n t s (48).

There was a 4 2 %

reduction i n circulating leucocyte

vitamin C

levels o n the t h i r d p o s t o p e r a t i v e d a y , regardless of t h e extent of s u r g i c a l t r a u m a , s u g g e s t i n g a n i n c r e a s e d n e e d f o r the v i t a m i n d u r i n g s u r g e r y a n d the p o s t o p e r a t i v e p e r i o d . M o r e r e c e n t l y , some a t t e n t i o n w a s e x p e r i m e n t a l l y d i r e c t e d to m a i n t a i n i n g the i n t e g r i t y of the eye f o l l o w i n g i n d u c e d a l k a l i b u r n s i n r a b b i t s . A s c o r b a t e levels i n r a b b i t aqueous h u m o r r e m a i n d e p r e s s e d for 4 w e e k s f o l l o w i n g a n a l k a l i b u r n (49,50).

T h e i n c i d e n c e of c o r n e a l u l c e r a t i o n

r e s u l t i n g f r o m this t r a u m a c a n b e r e d u c e d f r o m 6 0 %

i n saline-treated


374

ASCORBIC

controls to 2 2 %

b y ascorbate

topical administration (50).

injection (49)

or f r o m 4 7 %

to 6 %

ACID

by

A l s o , ascorbate prevents l i g h t - i n d u c e d d a m

age to the o c u l a r lens c a t i o n p u m p i n rat eyes, i n v i t r o

(51).

B e c a u s e of c u r r e n t interest i n atherosclerosis, w e w i l l m e n t i o n some of the r e l a t i o n s h i p s b e t w e e n

a s c o r b i c a c i d a n d some of the

V i t a m i n C deficient g u i n e a p i g s h a v e e l e v a t e d

levels ( 5 2 ) .

M o r e r e c e n t l y , a r e d u c e d rate of c h o l e s t e r o l c a t a b o l i s m w a s

d e m o n s t r a t e d i n c h r o n i c a l l y deficient g u i n e a pigs (53, 5 4 ) . Downloaded by UNIV ILLINOIS URBANA-CHAMPAIGN on July 14, 2016 | http://pubs.acs.org Publication Date: June 1, 1982 | doi: 10.1021/ba-1982-0200.ch018

associated

phenomena.

vations w e r e m a d e i n h u m a n subjects ( 5 5 ) . atherosclerosis is p l a t e l e t a g g r e g a t i o n .

cholesterol

S i m i l a r obser

A n o t h e r factor of interest i n

I n one report, p l a t e l e t v i t a m i n C

levels w e r e s i g n i f i c a n t l y l o w e r i n d i a b e t i c s t h a n i n n o r m a l h u m a n s , a n d the a d d i t i o n of the v i t a m i n i n n o r m a l concentrations

to p l a t e l e t - r i c h

p l a s m a consistently r e d u c e d a g g r e g a t i o n , as d i d the i n g e s t i o n of 2 g of v i t a m i n C / d for 7 d i n v i v o ( 5 6 ) . those of decreased

C o u p l i n g these observations

with

c h o l e s t e r o l c a t a b o l i s m suggests that v i t a m i n C is a

b a s i c factor i n atherogenesis. I n another m e d i c a l s i t u a t i o n , osteogenesis i m p e r f e c t a ,

supplementa

t i o n w i t h v i t a m i n C at a l e v e l of 1-2 g / d ( t o subjects w i t h a s c o r b i c a c i d levels i n the n o r m a l r a n g e ) r e s u l t e d i n i n c r e a s e d p h y s i c a l a c t i v i t y a n d stamina, a n d i n reduced fracture incidence (57).

These

findings

remain

to be c o n f i r m e d . S u p p l e m e n t a t i o n w i t h v i t a m i n C , 5 0 0 - 1 0 0 0 m g / d , to f o r t y - f o u r p a i r s of m o n o z y g o t i c

t w i n s for 5 m o n t h s r e s u l t e d i n shorter a n d less severe

illness episodes i n g i r l s , a n d r e s u l t e d i n g r o w t h of a n average of 1.3 c m m o r e t h a n u n t r e a t e d controls ( 5 8 ) . these

T h e investigators are r e i n v e s t i g a t i n g

findings.

A n o t h e r o b s e r v a t i o n i n a d o u b l e b l i n d crossover t r i a l o n l e g u l c e r s i n i n d i v i d u a l s w i t h /^-thalassemia, s h o w e d a h i g h e r rate of either c o m plete or p a r t i a l h e a l i n g w i t h 3 g of a s c o r b i c period

a c i d / d over a n 8-week

(59).

T h e effects of stress o n the depression of s e r u m / l e u c o c y t e v i t a m i n C were recently summarized (60).

Included were

levels of

myocardial

i n f a r c t i o n , a n d other c o n d i t i o n s i n v o l v i n g p h y s i c a l , i n f e c t i v e , o r t r a u m a t i c insult, i n c l u d i n g c o l d v i r u s i n f e c t i o n , a n d intravenous tetracosactrin. A s s o c i a t e d w i t h t h e r e d u c e d ascorbate l e v e l i n m y o c a r d i a l i n f a r c t i o n w a s a n increased Cortisol l e v e l o v e r a p e r i o d of 56 d. T h e authors

recommended

1 g of a s c o r b i c a c i d / d for 1 m o n t h f o l l o w i n g the t r a u m a t i c event, w i t h a c o m m e n t c o n c e r n i n g the n e e d for a d d i t i o n a l s t u d y (60). P l a s m a ascorbate w a s also depressed f o l l o w i n g i v a d m i n i s t r a t i o n of a d r e n a l i n ; this depres sion w a s p r e v e n t e d b y p r i o r a d m i n i s t r a t i o n of p r o p r a n o l o l , a /^-blocker (61).

S m o k i n g not o n l y reduces b l o o d levels of v i t a m i n C (62,63),

but

increases the p r o p o r t i o n of the p o p u l a t i o n i n the s c o r b u t i c r a n g e of b l o o d values f o u r f o l d

(64).

T h e s e effects are p r o b a b l y c a u s e d b y

increased


18.

BRIN

375

Ascorbic Acid: Nutrition

Ascorbic Acid - American Chemical Society

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