Vitamins and Dental Caries - Advances in Chemistry (ACS Publications)

4

Vitamins and Dental Caries

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SAMUEL DREIZEN University of Texas Dental Science Institute at Houston, Houston, Tex. 77025

Vitamins contribute to both the pathogenesis and preven tion of dental caries. During the formative period, vitamins A, C, and D are essential for proper deposition and calcification of tooth structure. Posteruptively, the vitamin-dental caries relationship is mediated primarily through the oral acidogenic microorganisms. The Β vitamins nicotinic acid, pantothenic acid, and biotin are necessary growth factors for most if not all of the oral acidogenic flora. Some strains also require an exogenous source of thiamine and riboflavin. As components of the coenzymes which participate in ana erobic glycolysis, thiamine and nicotinic acid promote acid production by microbial action on locally retained ingested carbohydrates. Unfortunately, none of the Β vitamins can be deleted safely from the diet for caries prevention without impairment of human health.

The

vitamins are a group of diverse organic compounds which are dietary in origin and indispensable for human health and well being. Most function as integral parts of enzyme systems involved in essential metabolic processes. As such, they are required in relatively small amounts in sharp contrast to the dietary macro-nutrients which contribute primarily to the structural makeup of cells and tissues. Dental caries is a posteruptive disease of the teeth resulting from the action of cariogenic oral microorganisms on susceptible tooth struc ture in the presence of a suitable substrate and a favorable local environ ment. Various vitamins have been associated with the pathogenesis and prevention of dental caries. Some are caries-conducive; others cariesdeterrent. Some affect the caries process by their presence; others by their absence. Some have a preemptive influence which is exerted on the size, shape, and structure of the teeth. Others operate posteruptively by influencing the quantity and composition of the saliva and the makeup 33 Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

34 of

DIETARY

the

oral microbial

flora.

Evidence

C H E M I C A L S

of

the

D E N T A L

VS.

vitamin-dental

CARIES

caries

r e l a t i o n s h i p is d e t a i l e d i n this report. Vitamin

A

Effects of Deficiency. L a c k of v i t a m i n A w i l l p r o d u c e characteristic


a b n o r m a l i t i e s i n the shape a n d structure of d e v e l o p i n g teeth, p r o v i d e d the d e f i c i e n c y is c h r o n i c e n o u g h a n d severe e n o u g h . mediated

through

alterations

i n the

T h e effects

highly specialized

are

odontogenic

e p i t h e l i u m l e a d i n g to disturbances i n histo- a n d m o r p h o d i f f e r e n t i a t i o n . I n the rat, avitaminosis A i n d u c e s e n a m e l h y p o p l a s i a , i r r e g u l a r a n d a t y p i c a l d e n t i n f o r m a t i o n , a n d e p i t h e l i a l i n v a s i o n of the d e n t a l p u l p

(79).

I n m a n the p r i m a r y h i s t o p a t h o l o g y is a m e t a p l a s i a of t h e e n a m e l - f o r m i n g cells a n d a n a t r o p h y of the e n a m e l o r g a n w h i c h is m a n i f e s t e d c l i n i c a l l y as e n a m e l h y p o p l a s i a (11, 23).

A v i t a m i n o s i s A is a rare cause of e n a m e l

h y p o p l a s i a i n the h u m a n , since deficiencies of the degree a n d d u r a t i o n r e q u i r e d to p r o d u c e d e t e c t a b l e d e n t a l defects are u s u a l l y not c o m p a t i b l e w i t h l i f e . B l o c h (10)

s t u d i e d 64 b l i n d D a n i s h c h i l d r e n w i t h gross e v i -

d e n c e of severe v i t a m i n A d e f i c i e n c y d u r i n g i n f a n c y a n d f o u n d neither c o n s p i c u o u s a b n o r m a l i t i e s i n the f o r m , p o s i t i o n , a n d consistency of the teeth n o r a n i n c r e a s e d p r e d i s p o s i t i o n to d e n t a l caries. (85)

Similarly, Shourie

f o u n d no greater i n c i d e n c e of d e n t a l caries i n I n d i a n c h i l d r e n w i t h

s k i n a n d eye lesions suggestive of v i t a m i n A d e f i c i e n c y t h a n i n a d e q u a t e l y nourished ethnically identical children. P a y n t e r a n d G r a i n g e r (71)

successfully m o d i f i e d the genetic

tem-

p l a t e of tooth m o r p h o l o g y b y r e s t r i c t i n g p r e g n a n t rats to a synthetic diet deficient i n v i t a m i n A d u r i n g the t i m e the m o l a r teeth w e r e b e i n g f o r m e d i n t h e o f f s p r i n g . T h e p r o c e d u r e caused the d e v e l o p m e n t of s m a l l m o l a r teeth i n the y o u n g to a degree w h i c h exceeded variation.

T h e size differences

the range of n o r m a l

w e r e not a c c o m p a n i e d b y gross

surface defects, severe h i s t o l o g i c changes,

tooth

m e t a b o l i c derangements,

or

a n increased caries s u s c e p t i b i l i t y . T h e o n l y e v i d e n c e of a d i r e c t r e l a t i o n s h i p b e t w e e n

dental

caries

a n d c h r o n i c v i t a m i n A d e f i c i e n c y is s u p p l i e d b y S a l l e y , B r y s o n , a n d E s h l e m a n (76),

w h o o b t a i n e d a significant increase i n caries i n hamsters

g i v e n a synthetic diet d e v o i d of v i t a m i n A . T h e c a r i e s - p r o m o t i n g p o t e n t i a l of v i t a m i n A d e f i c i e n c y w a s a s c r i b e d to a greatly r e d u c e d s a l i v a r y flow p r e c i p i t a t e d b y the d e f i c i e n c y r e l a t e d loss of secretory a c i n i i n the major a n d m i n o r s a l i v a r y glands. X e r o s t o m i a a t t r i b u t a b l e to a k e r a t i n i z i n g m e t a p l a s i a a n d i n f l a m m a t o r y reaction i n b o t h the s a l i v a r y g l a n d a c i n i a n d ducts has b e e n d e s c r i b e d i n h u m a n v i t a m i n A d e f i c i e n c y (4).

Un-

f o r t u n a t e l y , details of the c a r i o g e n i c i t y of the xerostomia i n these cases are l a c k i n g .

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

4.

D R E I Z E N

Vitamins

and

Dental

Caries

35

Effects of Excess. D i e t a r y s u p p l e m e n t s of v i t a m i n A neither s t i m ulate n o r suppress the caries t e n d e n c y i n c h i l d r e n (21, b y D a y a n d S e d w i c k (21)

64).

In a study

at least 6000 U . S . P . units of v i t a m i n A i n -

gested d a i l y i n tablet f o r m together w i t h a d d e d v i t a m i n D f o r 15 m o n t h s not o n l y f a i l e d to h a v e a b e n e f i c i a l effect o n the caries i n c i d e n c e , b u t a f f o r d e d n o m e a s u r a b l e p r o t e c t i o n to the n e w l y e r u p t e d teeth.

I n rats,


a d d i t i o n of excessive amounts of w a t e r - s o l u b l e a n d f a t - s o l u b l e v i t a m i n s i n c l u d i n g v i t a m i n A d i d not alter s i g n i f i c a n t l y either the average n u m b e r or average extent of carious lesions i n a n i m a l s w h o s e t o o t h d e v e l o p m e n t was almost c o m p l e t e w h e n the s u p p l e m e n t s w e r e i n i t i a t e d Thiamine (Vitamin

(82).

Bj)

Effects of Deficiency. I n 1958 S h a r p e n a k (81) that a d e f i c i e n c y of cocarboxylase

r e v i v e d a n hypothesis

( t h i a m i n e p y r o p h o s p h a t e or d i p h o s -

p h o t h i a m i n e ) is a n i m p o r t a n t cause of d e n t a l caries because of a n acc u m u l a t i o n of p y r u v i c a c i d i n the d e n t a l a n d b o d y tissues.

This concept

lacks s u p p o r t i v e e v i d e n c e a n d is i n d i r e c t conflict w i t h studies b y R u s s e l l (75)

i n South Vietnam and Thailand and b y Afonsky (2)

China.

i n central

T h e y s h o w that c o n s u m p t i o n of a n u t r i t i o n a l l y i n a d e q u a t e t r a -

d i t i o n a l diet, l o w or deficient i n t h i a m i n e , is w h o l l y c o m p a t i b l e w i t h a l o w caries

prevalence.

Effects of Excess.

G o l l (34)

tested the s u p p o s i t i o n that t h i a m i n e

d e f i c i e n c y m a y be a n etiologic factor i n d e n t a l caries b y f e e d i n g cakes p r e p a r e d f r o m t h i a m i n e - r i c h ingredients to a s m a l l g r o u p of G e r m a n children.

T h e t h i a m i n e intake p e r c h i l d w a s thus increased b y 0.8 m g

per day.

N o r e d u c t i o n i n caries i n c i d e n c e was n o t e d i n the

p e r i o d of s u p p l e m e n t a t i o n .

A g a p o v a (3)

9-month

o b t a i n e d a decrease i n the

d e n t a l caries attack rate i n some of 75 c h i l d r e n g i v e n a d i e t a r y a d d i t i v e of 2 m g t h i a m i n e d a i l y f o r 2 years.

T h e decrease w a s a t t r i b u t e d to the

suppressive a c t i o n of t h i a m i n e o n the c a r i o g e n i c m i c r o o r g a n i s m s . m i n e has b e e n f o u n d to be bacteriostatic w h e n a d d e d to s a l i v a in

Thiavitro

at a l e v e l of 200 /xgrams per m l . , a c o n c e n t r a t i o n w h i c h far exceeds the 0.2 to 1.4 /ngrams p e r 100 m l . n o r m a l l y present i n h u m a n s a l i v a (8,

30).

I n contrast, w h e n present at a l e v e l of 2 /xgrams p e r m l . i n a c h e m i c a l l y d e f i n e d c o m p l e t e synthetic m e d i u m , t h i a m i n e is g r o w t h - p r o m o t i n g rather t h a n bacteriostatic f o r some strains of o r a l acidogens Riboflavin

(Vitamin

(25).

B) 2

Effects of Deficiency. A s s h o w n b y d e n t a l surveys i n the U n i t e d States ( 5 5 ) , G u a t e m a l a (46), N i g e r i a (91), S o u t h V i e t n a m a n d T h a i l a n d ( 7 5 ) , a d i e t deficient i n r i b o f l a v i n is not necessarily c o n d u c i v e to d e n t a l


36

DIETARY

C H E M I C A L S

VS.

D E N T A L

CARIES

d e c a y . Subjects w i t h s u b s t a n d a r d r i b o f l a v i n intakes a n d c l i n i c a l e v i d e n c e of t h e d e f i c i e n c y state w e r e f o u n d to h a v e a caries p r e v a l e n c e w h i c h was no higher a n d often m u c h lower than i n nutritionally superior cont r o l g r o u p s i n t h e same r e g i o n . A l t h o u g h r i b o f l a v i n is a n u t r i t i o n a l essent i a l f o r some strains of o r a l l a c t o b a c i l l i , most w i l l tolerate a r i b o f l a v i n - f r e e synthetic m e d i u m w h i c h is c o m p l e t e i n a l l other n u t r i t i o n a l

essentials


(25,51). Effects of Excess. I n c l u s i o n of r i b o f l a v i n i n t h e d i e t o f rats i n amounts f a r i n excess of t h e i r n u t r i t i o n a l needs does n o t alter t h e i r s u s c e p t i b i l i t y to d e n t a l caries

(82).

T h e r e h a v e b e e n n o c o m p a r a b l e studies o n t h e

h u m a n level.

Nicotinic

Acid

(Niacin)

Effects of Deficiency. R e p o r t s f r o m v a r i o u s parts o f t h e w o r l d i n d i cate that e n d e m i c p e l l a g r i n s h a v e a l o w i n c i d e n c e o f d e n t a l caries 49, 74, 77).

(19,

T h e r e is c o n s i d e r a b l e e v i d e n c e that t h e l o w caries p r e v a l e n c e

a n d t h e n i c o t i n i c a c i d d e f i c i e n c y p r o d u c t i v e of p e l l a g r a are i n t e r r e l a t e d rather t h a n fortuitous.

N i c o t i n i c a c i d has p r o v e d to b e a n i r r e p l a c e a b l e

nutritional factor for the oral lactic a c i d - p r o d u c i n g bacteria N i c o t i n i c a c i d a m i d e acts as t h e f u n c t i o n a l g r o u p of

I a n d I I , e n z y m e s necessary f o r c o n v e r t i n g f e r m e n t a b l e to a c i d residues.

(25, 5 1 ) .

codehydrogenases carbohydrates

W i t h i n p h y s i o l o g i c l i m i t s , the a m o u n t of a c i d p r o d u c -

t i o n i n saliva—glucose m i x t u r e s , in vitro, is r e l a t e d d i r e c t l y t o t h e n i c o t i n i c a c i d content of t h e s a l i v a s a m p l e (24).

A d d i t i o n of antimetabolites of

n i c o t i n i c a c i d to s u c h m i x t u r e s c o m p l e t e l y i n h i b i t s a c i d f o r m a t i o n ( 2 5 , 53).

I n c o r p o r a t i o n of a m e t a b o l i c antagonist of n i c o t i n i c a c i d i n a n ex-

p e r i m e n t a l c a r i o g e n i c d i e t f e d w e a n l i n g rats f o r 150 days r e d u c e d t h e caries t e n d e n c y i n these a n i m a l s s i g n i f i c a n t l y (26).

Conversely, deletion

of n i c o t i n i c a c i d f r o m a n u t r i t i o n a l l y b a l a n c e d c a r i e s - p r o d u c i n g hamster d i e t r e s u l t e d i n a r e d u c t i o n i n caries i n c i d e n c e to a p p r o x i m a t e l y half that of t h e c o n t r o l g r o u p

(68).

Effects of Excess. K o s e r a n d K a s a i ( 5 2 ) f o u n d that c o m p a r a t i v e l y h u g e quantities of n i c o t i n i c a c i d of t h e o r d e r of 10,000 times t h e n u t r i t i o n a l r e q u i r e m e n t w i l l p r e v e n t c o m p l e t e l y t h e g r o w t h of n i c o t i n i c a c i d d e p e n d e n t b a c t e r i a in vitro.

E x p e r i m e n t a l l y , excessive amounts of n i c o -

t i n i c a c i d a n d other B v i t a m i n s increase t h e caries i n c i d e n c e i n hamsters (32)

a n d d o n o t influence caries s u s c e p t i b i l i t y i n rats (82).

Although

massive doses of n i c o t i n i c a c i d are b e i n g u s e d presently i n t r e a t i n g some cases o f h y p e r c h o l e s t e r e m i a i n m a n , there h a v e been n o reports of t h e effect of this t h e r a p y o n t h e h u m a n d e n t i t i o n .


4.

Vitamins

D R E I Z E N

Pyridoxine

(Vitamin

and

Dental

Caries

37

B) 6

Effects of Deficiency. T h e p o s s i b i l i t y of a r e l a t i o n s h i p b e t w e e n p y r i d o x i n e a n d d e n t a l caries w a s a d v a n c e d b y R i n e h a r t a n d G r e e n b e r g

(73)

w h o o b s e r v e d that m o n k e y s m a i n t a i n e d o n l o n g t e r m p y r i d o x i n e - d e f i c i e n t diets d e v e l o p extensive d e n t a l caries.

The pyridoxine deficiency-dental


caries axis w a s a p p a r e n t o n l y after a m i n i m u m of 2 years of exposure to the deficient diets, w i t h l i t t l e or n o adverse d e n t a l effects n o t e d d u r i n g the first 24 s t u d y m o n t h s .

Strean a n d c o - w o r k e r s ( 9 0 )

restricted small

groups of hamsters to a c a r i o g e n i c d i e t w i t h a n d w i t h o u t a d d e d p y r i d o x i n e ( 5 0 m g / 1 0 0 grams d i e t ) f o r 10 m o n t h s a n d o b t a i n e d a significant r e d u c t i o n i n f r e q u e n c y a n d extent of caries i n the p y r i d o x i n e - s u p p l e m e n t e d g r o u p . L a t e r Strean et al. (89)

subjected hamsters to c a r i o g e n i c

diets l o w i n p y r i d o x i n e (0.5 p p m ) a n d h i g h i n p y r i d o x i n e (10

ppm)

f o r 7 m o n t h s a n d f o u n d a significant p y r i d o x i n e - a s s o c i a t e d d i m i n u t i o n i n caries f r e q u e n c y for the l o w e r teeth b u t not f o r the u p p e r teeth.

The

d i s t i n c t i o n i n the locale of caries p r o t e c t i o n w a s a s c r i b e d to differences i n the p y r i d o x i n e content of the s a l i v a i n various parts of the m o u t h , b u t n o c h e m i c a l e v i d e n c e w a s offered to s u p p o r t this c o n t e n t i o n . Effects of Excess. T h e caries p r e v e n t i v e p o t e n t i a l of p y r i d o x i n e has b e e n tested i n a n i m a l s a n d i n m a n w i t h e q u i v o c a l results. W y n n , H a l d i , a n d L a w (94)

i n c l u d e d r e l a t i v e l y large amounts of p y r i d o x i n e ( u p to 100

p p m ) i n a s y n t h e t i c h i g h sucrose d i e t o r i g i n a l l y a d e q u a t e i n p y r i d o x i n e content.

T h e a d d e d p y r i d o x i n e f a i l e d to r e d u c e the c a r i o g e n i c i t y of the

test d i e t w h e n f e d to rats of a caries-susceptible S t e i n m a n a n d H a r d i n g e (87)

strain.

In

contrast,

a t t a i n e d a n o t a b l e r e d u c t i o n i n caries i n -

c i d e n c e w h e n rats w e r e g i v e n a r a t i o n representative

of the t y p i c a l

A m e r i c a n d i e t s u p p l e m e n t e d w i t h p y r i d o x i n e to the extent of 16 m g per k g food. I n a s m a l l p i l o t s t u d y , Strean et al.

(89)

achieved a 40%

reduction

i n n e w carious lesions i n 14 c h i l d r e n , 10 to 15 years o l d , g i v e n lozenges c o n t a i n i n g 3 m g p y r i d o x i n e t h r i c e d a i l y f o r 1 year. T h e reference g r o u p w a s c o m p r i s e d of 14 c h i l d r e n g i v e n p l a c e b o lozenges. (18)

Cohen and Rubin

u s e d a n i d e n t i c a l testing p r o c e d u r e i n 120 test c h i l d r e n a n d

129

c o n t r o l c h i l d r e n , 11 to 14 years of age, for 1 year a n d r e p o r t e d a slight suppressive effect of the p y r i d o x i n e lozenges o n d e n t a l caries.

T h e dif-

ference b e t w e e n the caries attack rates i n the p y r i d o x i n e a n d p l a c e b o g r o u p s w a s not, h o w e v e r , statistically significant. I n adults the effects of p y r i d o x i n e s u p p l e m e n t s o n d e n t a l experience has b e e n tested a n d Schenone (45).

caries

i n pregnant w o m e n by H i l l m a n , C a b a u d ,

S t a r t i n g w i t h the 4 t h m o n t h of p r e g n a n c y , 198 r a n -

d o m l y selected p r e g n a n t w o m e n w e r e g i v e n 20 m g p y r i d o x i n e once d a i l y i n c a p s u l e f o r m , 169 w e r e g i v e n a total of 20 m g p y r i d o x i n e t h r i c e d a i l y


38

DIETARY

C H E M I C A L S

VS.

D E N T A L

CARIES

i n l o z e n g e f o r m , a n d 173 r e c e i v e d p l a c e b o p r e p a r a t i o n s a n d s e r v e d as controls.

E a c h regimen was f o l l o w e d u n t i l parturition. T h e group not

g i v e n a d d e d p y r i d o x i n e h a d a n average D M F increase of 1.42 c o m p a r e d w i t h 1.22 f o r t h e c a p s u l e g r o u p a n d 0.89 f o r t h e l o z e n g e g r o u p . T h e difference b e t w e e n t h e m e a n D M F i n c r e m e n t s of the c o n t r o l a n d c a p s u l e g r o u p s w a s n o t significant; that b e t w e e n t h e c o n t r o l a n d l o z e n g e g r o u p s


w a s significant. S t r e a n ( 8 8 ) attributes t h e caries-deterrent a c t i o n of p y r i d o x i n e to a n a l t e r a t i o n of t h e o r a l flora f r o m a p r e d o m i n a n t l y h o m o f e r m e n t a t i v e l a c t i c a c i d - p r o d u c i n g t y p e to a p r e v a l e n c e o f h e t e r o f e r m e n t a t i v e f o r m s w h i c h p r o d u c e less l a c t i c a c i d a n d m o r e v o l a t i l e e n d p r o d u c t s .

Since

h o m o f e r m e n t a t i v e f o r m s d o n o t a n d h e t e r o f e r m e n t a t i v e forms d o u t i l i z e p y r i d o x i n e , t h e a d d i t i o n of p y r i d o x i n e creates a c o m p e t i t i v e system w h i c h eventuates i n s u p p r e s s i n g t h e h e a v y a c i d p r o d u c e r s . P a r t i a l s u p p o r t f o r this c o n t e n t i o n is s u p p l i e d b y P a l a z z o , C o b e , a n d P l o u m i s ( 7 0 ) , w h o showed

that

addition

of p y r i d o x i n e i n concentrations

ranging from

1:2000 to 1:200,000 to s u i t a b l e m e d i a i n h i b i t s h o m o f e r m e n t a t i v e strains of t h e o r a l flora a n d p r o m o t e s g r o w t h o f t h e h e t e r o f e r m e n t a t i v e

types.

A l t h o u g h p y r i d o x i n e has b e e n s h o w n to b e bacteriostatic against

some

strains o f o r a l m i c r o o r g a n i s m s w h e n a d d e d to s a l i v a i n a c o n c e n t r a t i o n of 20 m g p e r 100 m l ( 8 ) , levels of 200 m g p e r 100 m l f a i l e d t o affect a c i d p r o d u c t i o n i n i n c u b a t e d s a l i v a - g l u c o s e mixtures ( 2 8 ) .

A proper

e v a l u a t i o n of t h e role of p y r i d o x i n e i n t h e caries process awaits m o r e intensive microbiologic, chemical, a n d clinical investigation.

Other B Vitamins O t h e r B v i t a m i n s w i t h a p o t e n t i a l role i n t h e caries process are biotin, pantothenic acid, folic acid, a n d inositol. B i o t i n a n d pantothenic a c i d resemble n i c o t i n i c a c i d i n that t h e y are essential f o r the g r o w t h a n d a c i d p r o d u c t i o n of o r a l l a c t o b a c i l l i , s t r e p t o c o c c i , s t a p h y l o c o c c i , a n d yeasts i n p u r e a n d m i x e d c u l t u r e ( 2 5 , 51).

M a k i l a ( 5 4 ) f o u n d that the

m e a n f o l i c a c i d content of resting w h o l e s a l i v a i n e d e n t u l o u s d e n t u r e wearers a n d patients w i t h teeth l a r g e l y d e s t r o y e d b y caries is almost three times greater t h a n that i n subjects w i t h slight caries a c t i v i t y . It w a s c o n c l u d e d that either a h i g h s a l i v a f o l i c a c i d l e v e l promotes t h e d e v e l o p m e n t of caries, o r the c a r i e s - p r e c i p i t a t i n g factor leads to a n increase i n saliva folic a c i d concentration.

Significant caries r e d u c t i o n s h a v e

been

o b t a i n e d i n rats f e d c a r i o g e n i c sugar diets c o n t a i n i n g 0 . 0 1 - 0 . 1 % i n o s i t o l (67).

A d d i t i o n of 1.4% p h o s p h o r y l a t e d i n o s i t o l to a b r e a d - g l u c o s e r a t

d i e t decreased t h e i n c i d e n c e o f d e n t a l caries b y a n average o f 7 7 % a n d the caries severity score b y a n average of 9 1 % ( 5 9 ) . Studies b y M c C a n n ,


4.

D R E I Z E N

Vitamins

and

Dental

39

Caries

B r a d y , a n d G i l l e n ( 5 8 ) i n d i c a t e that e n a m e l m a y p i c k u p p h o s p h a t e f r o m p h o s p h o r y l a t e d i n o s i t o l b y i o n exchange a n d that the increase i n e n a m e l p h o s p h a t e contributes to the anticaries effectiveness of this c o m p o u n d i n rats.


Vitamin C (Ascorbic

Acid)

Effects of Deficiency. E v i d e n c e that v i t a m i n C is essential f o r n o r m a l t o o t h d e v e l o p m e n t is d e r i v e d f r o m h i s t o l o g i c changes i n the c o n t i n u o u s l y f o r m i n g incisors of s c o r b u t i c g u i n e a pigs.

T h e s e range f r o m

d i s t u r b e d h i s t o d i f f e r e n t i a t i o n of the odontoblasts c u l m i n a t i n g i n a m o r p h o u s a n d i r r e g u l a r d e n t i n f o r m a t i o n to a cessation of d e n t i n d e p o s i t i o n a n d o v e r c a l c i f i c a t i o n of the p r e d e n t i n . A t r o p h i c changes i n the

enamel

e p i t h e l i u m m a y o c c u r i n the late stages g i v i n g rise to e n a m e l h y p o p l a s i a (13).

Boyle

(12)

studied deciduous and permanent

t o o t h germs

of

s c o r b u t i c infants a n d f o u n d n o a b n o r m a l i t i e s except f o r some s m a l l cysts a n d m i n u t e hemorrhages

i n a f e w specimens.

Teeth

from

scorbutic

adults s h o w p o r o t i c d e n t i n , p u l p a l h y p e r e m i a a n d e d e m a , a n d a l t e r e d secondary d e n t i n f o r m a t i o n

(93).

D e s p i t e the s t r u c t u r a l changes associated w i t h s c u r v y , W e s t i n w a s u n a b l e to demonstrate

any relationship between

(93)

v i t a m i n C defi-

c i e n c y a n d d e n t a l caries i n the g u i n e a p i g , m o n k e y , or m a n , n o r is there a n y significant c o r r e l a t i o n b e t w e e n

the v i t a m i n C content

of h u m a n

b l o o d , s a l i v a , or u r i n e a n d d e n t a l caries a c t i v i t y (15, 44, 8 0 ) .

Neverthe-

less, O t t (69)

m a i n t a i n s that d e n t a l caries c a n be e q u a t e d w i t h d i s t u r b e d

v i t a m i n C m e t a b o l i s m b u t offers little c l i n i c a l a n d no e x p e r i m e n t a l e v i dence to substantiate

this c l a i m .

H a n k e (39)

s u p p l e m e n t e d the

diets

of 323 c h i l d r e n w i t h a p i n t of orange juice a n d the juice of one l e m o n d a i l y a n d o b t a i n e d a n a u s p i c i o u s r e d u c t i o n i n the i n t e n s i t y of

caries.

A d m i n i s t r a t i o n of 90 m l . of orange juice d a i l y f a i l e d to sustain the r e d u c e d caries a c t i v i t y , c a s t i n g some d o u b t o n the specificity of a d e n t a l c a r i e s vitamin C deficiency relationship. Effects of Excess. V i t a m i n C has been s h o w n to be c a r i e s - p r o m o t i n g , caries-neutral, a n d c a r i e s - p r e v e n t i n g — t h e

specific role v a r y i n g w i t h the

p a r t i c u l a r investigator.

regards p h a r m a c o l o g i c a l l y ef-

T h u s , H a f e r (38)

fective doses of v i t a m i n C as c a r i o g e n i c since the a d m i n i s t r a t i o n of s u c h doses is f o l l o w e d i n a f e w weeks b y a rise i n l a c t o b a c i l l u s counts a n d b y a f a l l i n the n e u t r a l i z i n g p o w e r of the s a l i v a .

W h e n incorporated in

c a r i o g e n i c diets i n amounts r a n g i n g f r o m 0 . 5 - 2 . 5 % of the d a i l y r a t i o n , v i t a m i n C is w i t h o u t m e a s u r a b l e effect o n caries i n rats ( 5 0 ) sters ( 3 5 ) .

and in ham-

I n c h i l d r e n , G r a n d i s o n , Stott, a n d C r u i k s h a n k (36)

found

no significant m o d i f i c a t i o n i n the caries course of 20 c h i l d r e n g i v e n 200 m g v i t a m i n C d a i l y for 2 years.

D i e r k s (22)

r e p o r t e d that d a i l y doses


40

DIETARY

C H E M I C A L S

VS.

D E N T A L

CARIES

of 100 m g v i t a m i n C are p r o t e c t i v e against the s e c o n d a r y d e c a y w h i c h forms around

filling

m a r g i n s , as no s u c h lesions d e v e l o p e d i n c h i l d r e n

g i v e n v i t a m i n C f o r 1 year. T h e l a c k of a c o n t r o l g r o u p a n d the f a i l u r e to influence p r i m a r y caries l i m i t s the v a l u e a n d a p p l i c a b i l i t y of these findings.


Vitamin

D

Effects of Deficiency. ficiency

T h e changes i n d u c e d b y a v i t a m i n D

de-

d u r i n g the f o r m a t i v e p e r i o d of the teeth v a r y w i t h the e x p e r i -

m e n t a l a n i m a l . I n a l l v i t a m i n D - d e p e n d e n t species, the first a n d most p r o m i n e n t d e f i c i e n c y c h a n g e is a l i n e of d i s t u r b e d c a l c i f i c a t i o n i n the dentin.

I n the severe cases this is f o l l o w e d b y a r e t a r d a t i o n of d e n t i n

f o r m a t i o n a n d a f a i l u r e of c a l c i f i c a t i o n of the p r e d e n t i n . I n the rat, e n a m e l f o r m a t i o n a n d c a l c i f i c a t i o n are unaffected b y a v i t a m i n D

deficiency,

b u t g u i n e a p i g s , dogs, a n d m a n m a y d e v e l o p h y p o p l a s t i c e n a m e l M e l l a n b y (61)

(40).

was the first to suggest that teeth w i t h i m p e r f e c t i o n s i n

the e n a m e l surface are m o r e susceptible to caries t h a n teeth w i t h o u t s u c h defects. refuted

(21,

T h i s concept has b e e n b o t h s u p p o r t e d (9, 20, 86),

w i t h M i i h l e m a n n (65)

expressing the

63)

and

contemporary

o p i n i o n that w h i l e s t r u c t u r a l irregularities a n d h y p o p l a s i a of the e n a m e l per

se d o not seem to increase caries s u s c e p t i b i l i t y , t h e y d o f a v o r post-

e r u p t i v e p l a q u e adherence a n d p o s s i b l y caries attack o w i n g to increased roughness. W h e t h e r r a c h i t i c c h i l d r e n have a greater t e n d e n c y to d e n t a l d e c a y t h a n n o n r a c h i t i c c h i l d r e n as has b e e n p r o c l a i m e d b y some (27, d i s p u t e d b y others M e l l a n b y (62)

(43,

84)

is s t i l l u n r e s o l v e d .

i m p l y that a n adequate

29)

and

N u m e r o u s studies

by

v i t a m i n D i n t a k e d u r i n g the

p e r i o d of tooth f o r m a t i o n i n c h i l d r e n is associated w i t h a r e d u c e d caries incidence.

A t t e m p t s to establish a r e l a t i o n s h i p b e t w e e n

dental

caries

a n d the v i t a m i n D content of the diet have been u n s u c c e s s f u l (95).

Di-

rect e v i d e n c e that h y p o p l a s i a is caused b y a d e f i c i e n c y of v i t a m i n D or that adequate v i t a m i n D per

se w i l l p r e v e n t h y p o p l a s i a or r e d u c e

i n c i d e n c e of d e n t a l caries is s t i l l l a c k i n g Effects of Excess.

the

(40).

T h e use of v i t a m i n D s u p p l e m e n t s to

control

d e n t a l caries is b e c l o u d e d b y a n inconsistency of results a n d i n t e r p r e t a tions.

C l a i m s for a caries-preventive

a c t i o n of v i t a m i n D range

from

u n m i t i g a t e d effectiveness regardless of age, diet, a n d f o r m a d m i n i s t e r e d (57)

to those t e m p e r e d b y s u c h l i m i t a t i o n s as: ( a ) v i t a m i n D p r o d u c e s

a substantial decrease i n the d e n t a l caries experience of c h i l d r e n w h e n g i v e n b e t w e e n 3 a n d 10 years of age b u t not w h e n g i v e n b e t w e e n a n d 16 years of age ( 5 ) ;

( b ) v i t a m i n D is m o r e b e n e f i c i a l against

w h e n a d d e d to a deficient diet t h a n to a w e l l b a l a n c e d d i e t (78);


11

caries (c)

4.

D R E I Z E N

Vitamins

and

Dental

Caries

41

v i t a m i n D decreases d e n t a l caries s u s c e p t i b i l i t y o n l y w h e n a d m i n i s t e r e d d u r i n g t h e f o r m a t i v e p e r i o d a n d not after a t o o t h has a l r e a d y e r u p t e d (6);

( d ) v i t a m i n D is m o r e effective against caries w h e n t a k e n as c o d

l i v e r o i l t h a n as i r r a d i a t e d ergosterol ( 5 6 ) .

Aebi (J)

reconciles studies

s h o w i n g a caries-deterrent a c t i o n of v i t a m i n D w i t h those w h i c h f a i l e d to c h a n g e the caries p a t t e r n (14,

21, 33, 48)

b y p o s t u l a t i n g that other


factors i n the caries p i c t u r e m a y s u p p l e m e n t or negate the influence of v i t a m i n D . I n a m o r e p r o s a i c v e i n , S h a w (83)

ascribes the lack of effect

of v i t a m i n D to a l a c k of a n existing d e f i c i e n c y i n the subjects g i v e n the s u p p l e m e n t s . I n contrast, V o l k e r (92)

suggests that the s p e c i a l bene-

fits n o t e d w i t h c o d l i v e r o i l as c o m p a r e d w i t h other p r e p a r a t i o n s

of

v i t a m i n D c o u l d b e e x p l a i n e d b y the l o c a l a c t i o n of the fats c o n t a i n e d t h e r e i n rather t h a n b y the f o r m of the v i t a m i n D . Vitamin

E

V i t a m i n E is essential for m a i n t a i n i n g the e n a m e l o r g a n of the rat incisor.

A d e f i c i e n c y leads to p r e m a t u r e a t r o p h y a n d e d e m a of

the

p a p i l l a r y layer, d e p i g m e n t a t i o n , h y p o p l a s i a , b i z a r r e a n a t o m i c f o r m s , ret a r d e d e r u p t i o n rate, a n d cyst f o r m a t i o n i n the adjacent c o n n e c t i v e tissue (66,

72).

T h e p a r e n c h y m a of the s a l i v a r y glands is r e p l a c e d b y fat cells

a n d fibrous c o n n e c t i v e tissue (66).

Because of its a n t i o x i d a n t c a p a c i t y ,

v i t a m i n E has b e e n tested against s u l c u l caries i n the rat.

L e v e l s u p to

0 . 5 % a-tocopherol i n the d i e t f a i l e d to i n h i b i t either caries or the g r o w t h of selected c a r i o g e n i c m i c r o o r g a n i s m s Vitamin

(47).

K

O f a l l presently k n o w n v i t a m i n s , o n l y v i t a m i n K prevents a c i d form a t i o n w h e n a d d e d to s a l i v a - g l u c o s e mixtures in vitro

(28).

The anti-

b a c t e r i a l properties of n a t u r a l a n d synthetic v i t a m i n K stem f r o m t h e i r q u i n o n e structure w h i c h acts as a n e n z y m e p o i s o n a n d not f r o m the v i t a m i n a c t i v i t y (7, 17).

T h e efficacy of v i t a m i n K i n c o n t r o l l i n g d e n t a l

caries b y i n h i b i t i n g the enzymes i n v o l v e d i n the m i c r o b i a l d e g r a d a t i o n of c a r b o h y d r a t e s has b e e n s t u d i e d i n rats, hamsters, a n d m a n . I n rats, p r o l o n g e d a d m i n i s t r a t i o n of synthetic v i t a m i n K i n c o n c e n trations r a n g i n g f r o m 0.005 to 0.8%

of a c a r i o g e n i c d i e t f a i l e d to exert

a m e a s u r a b l e effect o n the caries i n c i d e n c e (41).

I n hamsters, v i t a m i n K

p r e v e n t e d d e n t a l d e c a y w h e n 1 m g was a d d e d to the d i e t every second d a y or w h e n 1 m g w a s injected i n t r a p e r i t o n e a l l y every t h i r d d a y

(31).

I n m a n , c h e w i n g a stick of g u m c o n t a i n i n g 0.75 m g 2 - m e t h y l - l , 4 - n a p h t h o q u i n o n e s o d i u m bisulfite a d d i t i o n c o m p o u n d ( s y n t h e t i c v i t a m i n K )

for

at least 10 m i n u t e s after each m e a l for a p e r i o d of 18 m o n t h s b y 58 sub-


42

DIETARY

C H E M I C A L S

VS.

D E N T A L

CARIES

jects r e d u c e d the d e v e l o p m e n t of n e w carious lesions b y f r o m 60 to 8 0 % d e p e n d i n g o n the basis o f c o m p a r i s o n (16).

T h e v a l i d i t y of these c o n -

clusions has b e e n c h a l l e n g e d b y S h a w (83)

w h o a n a l y z e d the d a t a i n

the absence of a statistical e v a l u a t i o n b y the authors a n d b y a subsequent s t u d y i n w h i c h c h e w i n g a s y n t h e t i c v i t a m i n K - c o n t a i n i n g g u m after i n g e s t i o n of f o o d o r d r i n k h a d no caries-suppressive


and radiographic examination Vitamin

effect o n c l i n i c a l

(60).

P

Rutin, a compound w i t h vitamin P-like activity, and hesperidin, a n i n t e g r a l p a r t of the v i t a m i n P m o l e c u l e , e a c h w i t h a n t i o x i d a n t p r o p erties, h a v e b e e n i n v e s t i g a t e d f o r possible a n t i c a r i o g e n i c a c t i v i t y . N e i t h e r p r e v e n t e d caries i n rats w h e n i n c o r p o r a t e d i n a c a r i e s - i n d u c i n g d i e t n o r i n h i b i t e d the g r o w t h of selected b a c t e r i a u s u a l l y e n c o u n t e r e d i n the o r a l cavity.

I n a single t r i a l i n w h i c h rats w e r e f e d 0 . 5 %

h e s p e r i d i n , there

w a s a c t u a l l y a statistically significant increase i n caries score Vitamin

(47).

Mixtures

Effects of Deficiencies. G r e e n a n d H a r d e s (37) of short t e r m experiments

p e r f o r m e d a series

( 2 0 - 2 1 d a y s ) d e s i g n e d to test the effect of

m u l t i p l e v i t a m i n d e l e t i o n o n caries p r o d u c t i o n w i t h o u t i n d u c i n g f r a n k d e f i c i e n c y states. O m i s s i o n of a l l fat-soluble v i t a m i n s f r o m a c a r i o g e n i c d i e t w a s w i t h o u t effect o n the caries experience of w e a n l i n g a l b i n o rats, whereas a n absence of a l l w a t e r - s o l u b l e v i t a m i n s r e s u l t e d i n a significant decrease i n caries d e v e l o p m e n t .

T h e latter w a s a t t r i b u t e d , i n p a r t , to

a d i m i n i s h e d f o o d i n t a k e a n d d i s t u r b e d eating p a t t e r n since the rats f a i l e d to g r o w o n the w a t e r - s o l u b l e v i t a m i n deficient diet. Effects of Supplements. T h e a n t i c a r i o g e n i c effectiveness of m i x e d v i t a m i n preparations w a s i n v e s t i g a t e d i n a series of 436 h e a l t h y c h i l d r e n r a n g i n g i n age f r o m b i r t h to 5.5 years (42).

E a c h received a daily dietary

s u p p l e m e n t of 3000 to 4000 units v i t a m i n A , 400 units v i t a m i n D , 60 to 75 m g v i t a m i n C , 1.0 to 1.2 m g t h i a m i n e , 1.2 to 1.5 m g r i b o f l a v i n , a n d 8 to 15 m g n i a c i n a m i d e f o r 36 months. measurable fluoride

cariostatic

T h i s r e g i m e n f a i l e d to exert a

a c t i o n unless 0.5 to 1.0 m g

fluoride

as s o d i u m

w a s i n c o r p o r a t e d i n the d a i l y v i t a m i n s u p p l e m e n t .

Summary and

Conclusions

I n the p r e e m p t i v e p e r i o d , v i t a m i n s A , C , a n d D are essential f o r the p r o p e r d e p o s i t i o n a n d m i n e r a l i z a t i o n of t o o t h structure. A l t h o u g h w e l l f o r m e d teeth are not necessarily s y n o n y m o u s w i t h caries resistance,


4.

DREIZEN


43


such teeth may provide fewer opportunities for plaque attachment, plaque retention, and caries activity. In the posteruptive period, the vitamin-dental caries relationship is mediated primarily through the oral acidogenic flora. A l l cariogenic microorganisms are, to a certain extent, vitamin-dependent and require an exogenous supply of some or many of these nutrients. The spectrum of need varies with the particular organism. T h e Β vitamins nicotinic acid, pantothenic acid, and biotin are necessary growth factors for most, if not all, lactic acid bacteria. Some strains also require thiamine, ribo flavin, and folic acid. As components of the coenzymes involved i n anaerobic glycolysis, thiamine and nicotinic acid facilitate the production of organic acids by microbial action on retained ingested carbohydrates. Diets completely devoid of the vitamins which serve as essential growth factors for the oral acidogenic organisms or as glycolytic co enzyme components are caries-inhibitory. Unfortunately, these vitamins cannot be deleted safely from the diet without disastrous consequences to human health. Conversely, there is, as yet, no clear and uncontestable evidence that dietary supplements of any of the presently known vitamins is protective against human dental caries.

Literature Cited (1) (2) (3) (4) (5) (6) (7) (8) (9) (10) (11) (12) (13) (14) (15) (16) (17) (18) (19) (20) (21) (22) (23)

Aebi, H . , Nutr. Dieta 1964, 5, 82. Afonsky, D., J. Dental Res. 1951, 30, 53. Agapova, Ο. I., Stomatologiya 1954, 33, 17. Allington, Η. V., Arch. Dermatol. Syphilis 1950, 62, 829. Anderson, P. G., Williams, C. H . M . , Halderson, H . , Summerfeldt, C., Agnew, R. G., J. Am. Dental Assoc. 1934, 21, 1349. Armstrong, W . D.,J.Dental Res. 1948, 27, 376. Armstrong, W . D., Knutson, J. W., Proc. Soc. Exptl. Biol. & Med. 1943, 52, 307. Balogh, K., Petrucz, K., Angyal, J., J. Dental Res. 1960, 39, 886. Bibby, B. G., J. Dental Res. 1943, 22, 218. Bloch, C. E., Am. J. Diseases Children 1931, 42, 263. Boyle, P. E., J. Dental Res. 1933, 13, 39. Boyle, P. E., J. Dental Res. 1934, 14, 172. Boyle, P. E . , Wolbach, S. B., Bessey, Ο. Α., J. Dental Res. 1936, 15, 331. Bruszt, P., Oesterr. Z. Stomatol. 1958, 55, 72. Burrill, D . Y., J. Dental Res. 1942, 21, 330. Burrill, D . Y., Calandra, J. C., Tilden, Ε. B., Fosdick, L. S., J. Dental Res. 1945, 24, 273. Calandra, J. C., Fancher, Ο. E . , Fosdick, L. S., J. Dental Res. 1944, 23, 31. Cohen, Α., Rubin, C., Bull. Phila. County Dental Soc. 1958, 22, 84. Corkill, N. L., Lancet 1934, 1, 1387. Davies, J. N., Brit. Dental J. 1939, 67, 66. Day, C. D . M . , Sedwick, Η. J., J. Nutr. 1934, 8, 309. Dierks, K., Zahnaerztl. Rundschau. 1943, 52, 645. Dinnerman,M.,Oral Surg. Oral Med. Oral Pathol. 1951, 4, 1024.



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DIETARY C H E M I C A L S VS. D E N T A L CARIES

(24) Dreizen, S., Reed, A . I., Spies, T. D., Intern. Z. Vitaminforsch. 1951, 22, 396. (25) Dreizen, S., Spies, T. D., J. Dental Res. 1953, 32, 65. (26) Dreizen, S., Spirakis, C. N., Stone, R. E . , Intern. Z. Vitaminforsch. 1963, 33, 321. (27) Eliot, M . M . , Souther, S. P., Anderson, B. G., Arnim, S. S., Am. J. Diseases Children 1934, 48, 713. (28) Fancher, O. E., Calandra, J. C., Fosdick, L . S., J. Dental Res. 1944, 23, 23. (29) Firu, P., Diaconescu, M . , Cristea, M . , Gherga-Negrea, Α., Cristea, I., Stomatologia (Bucharest) 1965, 12, 139. (30) Fujishiro, I., Igaku To Seibutsagaku 1952, 23, 59. (31) Gebauer, H . , Deut. Zahnaerztl. Z. 1955, 10, 555. (32) Gebauer, H . , Plathner, C. H., Deut. Zahnaerztl. Z. 1959, 14, 1693. (33) Goll, H . , Wien. Klin. Wochenschr. 1939, 52, 35. (34) Goll, H . , Med. Klin. 1940, 26, 712. (35) Granados, H . , Glavind, J., Dam, H., J. Dental Res. 1949, 28, 670. (36) Grandison, W . B., Stott, L . B., Cruikshank, D . B., Brit. Dental J. 1942, 72, 237. (37) Green, R. M., Hartles, R. L . , Arch. Oral Biol. 1966, 11, 913. (38) Hafer, H . , J. Dentistry Belge 1959, 50, 187. (39) Hanke, M . T., "Diet and Dental Health," p. 142, The University of Chi cago Press, Chicago, 1933. (40) Hartles, R. L . , Slack, G. L., Proc. Nutr. Soc. 1959, 18, 79. (41) Hatton, Ε. H . , Dodds, Α., Hodge, H . C., Fosdick, L . S., J. Dental Res. 1945, 24, 283. (42) Hennon, D . K., Stookey, G. K., Muhler, J. C., J. Dentistry Children 1966, 33, 3. (43) Hess, A. F., Abramson, H . , Dental Cosmos 1931, 73, 849. (44) Hess, W . C., Smith, B. T., J. Dental Res. 1949, 28, 507. (45) Hillman, R. W., Cabaud, P. G., Schenone, R. Α., Am. J. Clin. Nutr. 1962, 10, 512. (46) Hurtate, Α., Scrimshaw, N. S., J. Dental Res. 1955, 34, 390. (47) Jordan, Η. V., Bowler, A . E . , Berger, N. D., J. Dental Res. 1961, 40, 878. (48) Jundell, I., Hanson, R., Sandberg, T., Acta Paediat. 1938, 23, 141. (49) Kniesner, A . H., Mann, A . W., Spies, T. D., J. Dental Res. 1942, 21, 259. (50) Konig, K. G., Mühlemann, H . R., Helv. Odontol. Acta 1964, 8, 72 suppl. 1. (51) Koser, S. Α., Fisher, B. J., J. Dental Res. 1950, 29, 760. (52) Koser, S. Α., Kasai, G. J., J. Bacteriol. 1947, 53, 743. (53) Krasse, B., Acta Odontol. Scand. 1954, 12, 173. (54) Mäkilä, Ε., Arch. Oral Biol. 1966, 11, 839. (55) Mann, A. W., Dreizen, S., Spies, T. D., Hunt, F . M . , J. Am. Dental Assoc. 1947, 34, 244. (56) McBeath, E . C., Verlin, W . Α., J. Am. Dental Assoc. 1942, 29, 1393. (57) McBeath, E . C., Zucker, T. F., J. Nutr. 1938, 15, 547. (58) McCann, M . C., Brady, R. R., Gillen, W . R., New Zealand Dental J. 1962, 58, 244. (59) McClure, F . J., J. Nutr. 1960, 72, 131. (60) Medical Department Professional Service Schools, Bull. U. S. Army Med. Dept. 1946, 5, 265. (61) Mellanby, M., Brit. Dental J. 1923, 44, 1. (62) Mellanby, M . , Med. Res. Council, Spec. Repts. Ser. (London) 1934, 191. (63) Mellanby, M., Brit. Med. J. 1940, 1, 1341. (64) Mellanby, M., Pattison, C. L., Brit. Med. J. 1928, 2, 1079. (65) Mühlemann, H . R., "Nutrition and Caries Prevention," G. Blix, Ed., p. 9, Almqvist and Wiksells, Upsalla, Sweden, 1965.



4.

DREIZEN


45

(66) Nelson, Μ. Α., Jr., Chaudry, A. P., J. Dental Res. 1966, 45, 1072. (67) Novotny, J., Cesk. Stomatol. 1960, 60, 350. (68) Orland, F . J., Hemmens, E . S., Harrison, R. W., J. Dental Res. 1950, 29, 512. (69) Ott, E., Int. Z. Vitaminforsch. 1958, 29, 83. (70) Palazzo, Α., Cobe, H . M . , Ploumis, Ε., Ν. Y. State Dental J. 1959, 25, 303. (71) Paynter, K. J., Grainger, R. M . , J. Can. Dental Assoc. 1956, 22, 519. (72) Pindborg, J. J., J. Dental Res. 1952, 31, 805. (73) Rinehart, J. F., Greenberg, L. D., Am. J. Clin. Nutr. 1956, 4, 318. (74) Roberts, S. R., "Pellagra," p. 109, C. V. Mosby Co., St. Louis, 1912. (75) Russell, A. J., J. Dental Res. 1963, 42, 233. (76) Salley, J. J., Bryson, W . F., Eshleman, J. R., J. Dental Res. 1959, 38, 1038. (77) Sandwith, F . M . , "The Medical Diseases of Egypt," p. 296, H. Kempton, London, 1905. (78) Schoenthal, L . , Brodsky, R. H., Am. J. Diseases Children 1933, 46, 91. (79) Schour, I., Massler, M . , Physiol. Rev. 1945, 25, 442. (80) Shannon, I. L., Gibson, W . Α., Arch. Oral Biol. 1964, 9, 371. (81) Sharpenak, A. E . , Stomatol. Moscow 1958, 37, 3. (82) Shaw, J. H . , Proc. Soc. Exptl. Biol. & Med. 1949, 70, 479. (83) Shaw, J. H . , Natl. Acad. Sci.—Natl. Res. Council 1952, Publ. 225, 415. (84) Shelling, D . H., Anderson, G. M . , J. Am. Dental Assoc. 1936, 23, 840. (85) Shourie, K. L., Indian J. Med. Res. 1942, 30, 561. (86) Staz, J., S. African Med. J. 1943, 17, 1. (87) Steinman, R. R., Hardinge, M . G., J. Dental Res. 1958, 37, 874. (88) Strean, L . P., Schweiz. Monatsschr. Zahnheilk. 1957, 67, 981. (89) Strean, L . P., Bell, F . T., Gilfillan, E . W., Emerson, G. Α., Howe, Ε. E . , Ν. Y. State Dental J. 1958, 24, 133. (90) Strean, L . P., Gilfillan, E . W., Emerson, G. Α., Ν. Y. State Dental J. 1956, 22, 325. (91) Tabrah, F. L., Science 1962, 138, 38. (92) Volker, J. F., " A Symposium on Preventive Dentistry," J. C. Muhler and M . K. Hine, Eds., p. 45, The C. V . Mosby Co., St. Louis, 1956. (93) Westin, G., Dental Cosmos 1925, 67, 868. (94) Wynn, W., Haldi, J., Law, M . L., J. Nutr. 1960, 70, 69. (95) Youmans, J. B., Patton, E . W., Sutton, W . R., Kern, R., Steinkamp, R., Am. J. Public Health 1944, 34, 1049. RECEIVED August 14, 1968.


Vitamins and Dental Caries - Advances in Chemistry (ACS Publications)

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