Dietary Chemicals vs. Dental Caries

2

Carbohydrates, Fats, and Dental Caries

WARD PIGMAN

Downloaded by CORNELL UNIV on August 23, 2016 | http://pubs.acs.org Publication Date: June 1, 1970 | doi: 10.1021/ba-1970-0094.ch002

Department of Biochemistry, New York Medical College, New York, N . Y. 10029

Dental caries results from attack on the tooth surface by microorganisms, especially in noncleansing areas. Dietary factors may influence this attack by acting on the tooth or the microorganisms. With experimental animals, dietary carbohydrates exert a pre- and post-eruptive cariogenic effect, whereas fats as a whole may mediate the post -eruptive effect. Comparisons of primitive man with man living under urban conditions have demonstrated a great enhancement in dental caries in modern man. Such studies and those with controlled populations have suggested that some types of carbohydrates are the main origin of the increased incidence of dental decay. In vitro studies using the artificial mouth have shown most common sugars to be potentially cariogenic.

Carbohydrate constituents usually provide the major source of energy in human diets. As starches, modified starches, and sugars, they also have been the dietary products most susceptible to industrial modification and application in products such as syrups, refined sugars, candies, gums, puddings, soft drinks, canned fruits, and other products. Since these products are produced and consumed mainly in highly industrialized countries, which also have high rates of dental decay, much interest has been shown in the relationship of such products to dental caries. Many investigations of various types have been carried out to determine whether a direct relationship exists between dietary carbohydrates and the incidence of dental caries. The number of such investigations is so great that they cannot be considered adequately in this review. As a result, the principal types of investigations w i l l be considered, and except for recent work, reference generally w i l l be given to secondary sources which discuss the subject more adequately and also give the original 7 Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

8

DIETARY

literature.

C H E M I C A L S

VS.

D E N T A L

CARIES

A v a l u a b l e b i b l i o g r a p h y o f recent research o n d e n t a l caries

has b e e n p r e p a r e d b y B r i s l i n a n d C o x (4). U n i v e r s a l agreement seems to exist o n t h e nature of t h e basic process i n v o l v e d i n d e n t a l caries.

I t consists of t h e attack b y t h e p r o d u c t s of

m e t a b o l i s m of o r a l b a c t e r i a

o n exposed surfaces

o f teeth, u s u a l l y o n

e n a m e l , b u t also o c c u r r i n g o n c e m e n t u m a n d exposed d e n t i n . T h e attack is thus b a s i c a l l y external, a l t h o u g h p o s s i b l y m o d i f i e d b y i n t e r n a l m e t a b o l i c influences.

D e n t a l caries i n i t i a l l y is n e a r l y a l w a y s h i g h l y l o c a l i z e d a n d

i n positions w h i c h are n o n c l e a n s i n g .

T h e d i s t r i b u t i o n of lesions i n t h e


m o u t h has a s i m i l a r p a t t e r n i n most persons, a n d t h e areas most c o m m o n l y affected are t h e pits a n d fissures of molars a n d p r e m o l a r s , i n t e r p r o x i m a l positions, a n d c e r v i c a l m a r g i n s .

T h e s e positions a c c u m u l a t e f o o d p a r t i -

cles, a n d p r e s u m a b l y are t h e best positions f o r t h e establishment of b a c t e r i a l plaques.

T h e c o m b i n a t i o n of f o o d m a t e r i a l a n d b a c t e r i a p r o v i d e

the attack factor i n d e n t a l caries.

T h e attack, h o w e v e r , is m o d i f i e d b y

m a n y factors, some of w h i c h w i l l b e c o n s i d e r e d later. S a l i v a is r e l a t e d to d e n t a l caries as a b i o l o g i c a l fluid w h i c h washes out f e r m e n t a b l e substrates b e f o r e t h e y are m e t a b o l i z e d , d i l u t e s h a r m f u l b a c t e r i a l p r o d u c t s b e f o r e t h e y attack t h e t o o t h surface, p o s s i b l y repairs i n c i p i e n t carious lesions t h r o u g h r e m i n e r a l i z a t i o n , a n d modifies t h e t o o t h surface b y p r o v i d i n g t h e elements n e e d e d f o r t h e s e c o n d a r y c u t i c l e of the

tooth.

I n a d d i t i o n , its i m m u n e b o d i e s

m a y affect t h e b a c t e r i a l

population. P^re-Eruptive and Systemic Effects R e l a t i v e l y little is k n o w n , except c o n c e r n i n g fluorides, of t h e d i e t a r y effects that take p l a c e d u r i n g t o o t h f o r m a t i o n o r w h i c h result f r o m gene r a l m e t a b o l i c influences.

H o w e v e r , K i t e , S h a w , a n d Sognnaes (23,

30)

s h o w e d that rats f e d o n c a r b o h y d r a t e - r i c h diets d e v e l o p e d caries, b u t a g r o u p to w h i c h t h e same diet w a s g i v e n b y s t o m a c h t u b e d e v e l o p e d n o caries.

T h i s indicates that t h e effect w a s p r i m a r i l y a l o c a l o n e at t h e

t o o t h surface. S e v e r a l studies h a v e b e e n c a r r i e d o u t w i t h different types of a n i m a l s g i v e n h i g h - c a r b o h y d r a t e diets at v a r i o u s stages of t o o t h f o r m a t i o n a n d m a t u r a t i o n (23, 28).

Sognnaes ( T a b l e I ) f o u n d that a n i m a l s f e d s u c h

diets d u r i n g p r e g n a n c y h a d p r o g e n y w i t h h i g h e r caries t h a n those f e d " n a t u r a l " diets.

susceptibility

S i n c e t h e i n d i v i d u a l m o l a r teeth of rats

a n d hamsters are f o r m e d a n d erupt at different p e r i o d s , the effect o f a h i g h - c a r b o h y d r a t e diet d u r i n g t h e p e r i o d of t o o t h f o r m a t i o n a n d subseq u e n t m a t u r a t i o n also c o u l d b e s t u d i e d . T h e s e experiments s h o w e d t h e existence of a p e r i o d of h i g h caries s u s c e p t i b i l i t y f o l l o w i n g e r u p t i o n of

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

2.

P I G M A N

Carbohydrates,

Fats, Dental

Caries

9

the teeth a n d a g r a d u a l m a t u r a t i o n to a less susceptible c o n d i t i o n [ F i n n , Klapper and Volker (28)]. Table I.

Comparison of Caries Susceptibility in Hamsters, Rats, and Mice When " B r e d " on Stock Diet vs. Purified D i e t 0

Pregnancy. No, of and Animals Lactation


Species

Posteruptive

Average Caries

Diet

Period, Months

Molars Affected

Incidence

Areas Affected

Caries Score

Hamsters Rats Mice

6 12 15

Stock Stock Stock

Purified Purified Purified

4 4 4

4.6 0 0

5.3 0 0

6.1 0 0

Hamsters Rats Mice

3 10 21



2 2 2

9.0 2.4 0.4

31.6 2.7 0.5

48.0 2.7 0.5

° From Sognnaes (30). Copyright by the American Dental Association. Reprinted by permission. T h e effects o f p r e n a t a l n u t r i t i o n o n t h e o r a l structures h a v e r e v i e w e d b y L a r s o n (19). S h a w a n d G r i f f i t h s (26,27)

been

reported many mal-

f o r m e d t h i r d m o l a r s i n y o u n g rats w h o s e mothers h a d b e e n o n diets w i t h a protein-to-sucrose r a t i o of 8 : 8 3 , as c o m p a r e d w i t h those f r o m mothers h a v i n g a r a t i o of 24:67. H a l l o w a y et al. (15), i n a d d i t i o n t o m o r p h o l o g i c a l changes, f o u n d that t h e y o u n g o f m o t h e r rats o n a high-sucrose d i e t h a d teeth less resistant t o caries. Effects on Mature Teeth T h r e e g e n e r a l p r o c e d u r e s h a v e b e e n u s e d f o r studies of t h e influence of d i e t a r y c a r b o h y d r a t e s a n d fats o n t h e i n c i d e n c e o f t o o t h d e c a y .

These

are h u m a n n u t r i t i o n a l studies w i t h g r o u p s h a v i n g different diets, a n i m a l studies w i t h c o n t r o l l e d diets, a n d in vitro

procedures.

These w i l l be

d i s c u s s e d separately. H u m a n Nutritional Studies (1, 23, 30).

M a n y studies h a v e

been

made using h u m a n populations. These include institutionalized people o n c o n t r o l l e d diets, persons o n restricted diets ( d i a b e t i c s , f o r e x a m p l e ) , a n d p e o p l e l i v i n g u n d e r c o n d i t i o n s n o t affected b y m o d e r n i n d u s t r i a l i z a t i o n (e.g., E s k i m o s , I n d i a n s , e t c . ) . S u c h studies are d i f f i c u l t t o c o n d u c t a n d to i n t e r p r e t i n r e l a t i o n t o c a u s a l relationships. T h e y s h o w that gene r a l l y persons l i v i n g u n d e r p r i m i t i v e c o n d i t i o n s h a v e l o w caries

rates;

the same p o p u l a t i o n types l i v i n g i n u r b a n areas w i t h contact w i t h m o d e r n i n d u s t r i a l p r o d u c t s h a v e m u c h h i g h e r average rates of caries. Since m a n y factors a r e different f o r s u c h u r b a n a n d r u r a l c o n d i t i o n s , a d i r e c t r e l a t i o n to d i e t a r y constituents cannot b e d e m o n s t r a t e d .


10

DIETARY

C H E M I C A L S

VS.

D E N T A L

CARIES

O n e h u m a n s t u d y r e q u i r e s s p e c i a l attention. T h i s s t u d y w a s c a r r i e d o u t at the V i p e h o l m M e n t a l H o s p i t a l at L u n d , S w e d e n , a n d has b e c o m e k n o w n as the V i p e h o l m D e n t a l C a r i e s S t u d y (20, 3 2 ) .

This carefully

c o n d u c t e d s t u d y s h o w e d a f a i r l y clear r e l a t i o n s h i p b e t w e e n c a r b o h y d r a t e p r o d u c t s of some types a n d d e n t a l caries experience.

It w i l l b e d i s c u s s e d

i n m o r e d e t a i l i n a later section. T h e effects of fats i n h u m a n d i e t a r y studies h a v e b e e n s u m m a r i z e d by Volker and Caldwell (35).

T h e g e n e r a l i m p r e s s i o n is that diets r i c h

i n fats are l o w i n c a r i o g e n i c i t y . T h u s , n o m a d i c E s k i m o s o n p r o t e i n - f a t


diets, c o m p o s e d of as m u c h as 6 5 %

fat, h a d l o w caries i n c i d e n c e .

The

results of several c l i n i c a l studies o n c o n t r o l l e d g r o u p s w e r e i n t e r p r e t e d s i m i l a r l y , b u t , as w i t h most of the studies o n h i g h - c a r b o h y d r a t e diets, t h e interpretations h a v e q u e s t i o n a b l e significance. Animal Studies ( 2 8 ) .

M a n y studies of d i e t a r y c o m p o s i t i o n i n r e l a -

t i o n to d e n t a l caries h a v e b e e n c a r r i e d o u t w i t h e x p e r i m e n t a l a n i m a l s . H a m s t e r s a n d rats h a v e b e e n u s e d p r i n c i p a l l y , b u t m o n k e y s a n d other a n i m a l s also h a v e b e e n e m p l o y e d . T h e carious lesions p r o d u c e d i n rats a n d hamsters seem to b e s i m i l a r to those p r o d u c e d i n h u m a n s , a l t h o u g h i n the e a r l y w o r k w i t h rats t h e caries seemed to b e r e l a t e d to coarse diets a n d the f o r m a t i o n of cracks i n the t o o t h structure. T h e caries r a t e c a n b e g r e a t l y i n c r e a s e d b y p r i o r r e m o v a l of the m a i n s a l i v a r y glands. T h e use of " n a t u r a l d i e t s " s u c h as P u r i n a C h o w u s u a l l y r e s u l t e d i n l o w caries rates. W h e n a m a j o r p a r t of the d i e t w a s c o m p o s e d of starches, sucrose, or dextrose, d e n t a l caries w a s extensive, a l t h o u g h some studies h a v e f o u n d starches a n d dextrins to b e less c a r i o g e n i c t h a n sucrose or dextrose

[See

Finn, Klapper, and Volker (28)].

Klapper and Volker

f o u n d fructose a n d e s p e c i a l l y s o r b i t o l to b e less c a r i o g e n i c t h a n sucrose. M c C l u r e (28)

f o u n d that the c a r i o g e n i c effect of m i l k p r o d u c t s a n d

processed cereals c o u l d b e g r e a t l y i n c r e a s e d b y h e a t treatments.

These

results, a r i s i n g f r o m d e s t r u c t i o n of l y s i n e , e m p h a s i z e the n e e d f o r k n o w l edge of the effects of p r o c e s s i n g treatments o n the possible c a r i o g e n i c i t y of f o o d p r o d u c t s . T h e c a r i o g e n i c i t y of d r y w h e y p o w d e r s also suggests that lactose is p r o b a b l y c a r i o g e n i c i n a n i m a l experiments. Instead of e x p e r i m e n t a l diets, S t e p h a n (31)

a d d e d h u m a n foods

(53

i n a l l ) to b a s i c diets of rats a n d c o m p a r e d the caries experience to that o f a n i m a l s r e c e i v i n g diets of k n o w n c a r i o g e n i c i t y . A s a result, h e classified f o o d p r o d u c t s i n t o five g r o u p s , a c c o r d i n g to the a m o u n t of caries.

The

most extreme g r o u p was c o m p o s e d of foods r i c h i n c a r b o h y d r a t e s , especially fermentable

sugars.

T h e i n t e r p r e t a t i o n of a n i m a l experiments of this t y p e i n terms of h u m a n caries is f r a u g h t w i t h difficulties. T h e caries rate is v e r y h i g h as c o m p a r e d w i t h the u s u a l h u m a n rate.

O n e factor i n c r e a s i n g the rate

is the s m a l l size of r o d e n t teeth a n d the r e s u l t i n g t h i n e n a m e l .

Another


2.

P I G M A N

Carbohydrates,

Fats, Dental

Caries

11

is the constant " d i r t y " m o u t h ; s u c h a n i m a l s u s u a l l y h a v e the teeth b u r i e d i n s o l i d f o o d particles.

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

a n i m a l s , w h i c h also i n t r o d u c e s the p r o b l e m of c o m p a r i s o n s o f starches w i t h sucrose o r dextrose i n the absence of s a l i v a r y amylases. T h e a n i m a l diets u s u a l l y i n c l u d e starch as u n c o o k e d particles, different f r o m t h e g e l a t i n i z e d starches c o m m o n f o r h u m a n diets.

F o r a n i m a l experiments

of this t y p e , t h e attack forces c o u l d o v e r w h e l m a n y m i l d p r o t e c t i v e forces s u c h as possible s a l i v a c o m p o n e n t s or a n a t o m i c a l relations. T h u s , H a l d i et al. (13)

f o u n d that i n hamsters a h i g h sucrose d i e t p r o d u c e d a l a r g e r


caries score t h a n a s i m i l a r d i e t w i t h glucose, b u t f o r d e s a l i v a t e d a n i m a l s , the t w o diets gave s i m i l a r results. A n o t h e r m a j o r d i f f i c u l t y is that the v a r i o u s laboratories pass t h r o u g h p e r i o d s d u r i n g w h i c h the u s u a l c a r i o g e n i c diets d o not p r o d u c e

the

e x p e c t e d caries. T h i s v a r i a b i l i t y is p r o b a b l y e x p l a i n e d b y the o b s e r v a t i o n of F i t z g e r a l d a n d K e y e s [ M c D o n a l d ( 2 8 ) ]

that caries-inactive rodents

c o u l d b e c o n v e r t e d to caries-active a n i m a l s b y exposure to caries-active a n i m a l s o r t h e i r feces.

T h u s , a n a p p r o p r i a t e o r a l flora is r e q u i r e d f o r

caries p r o d u c t i o n . E a r l i e r , O r l a n d h a d d e m o n s t r a t e d that germ-free rats d i d not a c q u i r e caries w h e n f e d diets n o r m a l l y c a r i o g e n i c . S e v e r a l studies o f the effects of d i e t a r y fats o n caries i n c i d e n c e i n rats or hamsters h a v e b e e n s u m m a r i z e d b y V o l k e r (34).

T h e fats i n -

c l u d e d w e r e c o r n o i l , l a r d , arachis o i l , a n d h y d r o g e n a t e d arachis o i l . T h e s e studies s h o w e d a r e d u c e d i n c i d e n c e of caries i n c o m p a r i s o n w i t h the c o n t r o l diets.

Since the fats r e d u c e d the other c o m p o n e n t s of the

diet, the effect m a y not h a v e b e e n cariostatic, b u t i n s t e a d t h e result of d i l u t i o n of a c a r i o g e n i c c o m p o n e n t .

T h e u s u a l i n t e r p r e t a t i o n of these

experiments has b e e n that the fats f a v o r e d o r a l clearance, p e r h a p s b y f o r m i n g films o n the teeth. In V i t r o Laboratory

Procedures

A n u m b e r of l a b o r a t o r y p r o c e d u r e s h a v e b e e n u s e d to investigate the possible c a r i o g e n i c i t y of c a r b o h y d r a t e s a n d foodstuffs. A c i d Production and Plaque p H ( 3 5 ) .

W h e n h u m a n salivas, s a l i v a r y

d e b r i s , or s a l i v a r y m i c r o o r g a n i s m s are i n c u b a t e d w i t h m a n y sugars, starch p r o d u c t s , or foodstuffs

c o n t a i n i n g these c a r b o h y d r a t e s ,

the

solutions

r a p i d l y b e c o m e a c i d i c ( u s u a l l y p H 4 . 5 - 5 . 0 ) . S t a r c h p r o d u c t s a p p e a r to p r o d u c e a c i d m o r e s l o w l y t h a n the c o m m o n sugars. A m o d i f i c a t i o n of this m e t h o d f o r in vivo studies w a s d e s c r i b e d b y Stephan.

H u m a n subjects w e r e i n s t r u c t e d not to b r u s h t h e i r teeth f o r

several d a y s . T h e p H of t o o t h surfaces w a s t h e n m e a s u r e d b y t o u c h i n g t h e teeth w i t h a t i n y electrode ( a n t i m o n y o r glass) a n d w i t h a c a l o m e l electrode c o n t a c t i n g the s a l i v a i n the floor of the m o u t h . T h e m o u t h t h e n


12

DIETARY

C H E M I C A L S

VS.

D E N T A L

CARIES

was rinsed w i t h a solution containing a carbohydrate or suspended foodstuff. T h e p H o f t h e p l a q u e w a s m e a s u r e d at short t i m e intervals.

With

the c o m m o n sugars, a r a p i d decrease o f p H o c c u r r e d , f o l l o w e d u s u a l l y b y a s l o w r e t u r n t o t h e o r i g i n a l p H . Results g i v e n b y L u d w i g a n d B i b b y are s h o w n i n F i g u r e 1 .


(29)

2 MIN RINSE WITH 20% GLUCOSE. FIG SANDWICH COOKIE. FRENCH FRIED POTATOES. APPLE. COLA BEVERAGE.

IO. 15. 2Q 25. 30. 35. 4Q TIME IN MftJUTES.

From Sognnaes, R. F., Ed., "Chemistry and Prevention of Dental Caries," 1962. Courtesy of Charles C. Thomas, Publisher, Springfield, Illinois.

Figure 1. Effect of various foods on plaque pH, based on data by Ludwig and Bibby; taken from Jenkins (29) T h e a c t u a l results h a v e v a r i e d s o m e w h a t i n v a r i o u s u s i n g different c o n d i t i o n s .

investigations

T h e general p a t t e r n is f o r sugars s u c h as

dextrose a n d sucrose t o s h o w a r a p i d p H d r o p o f several units a n d r a p i d recovery.

S t a r c h p r o d u c t s a n d foods m a y s h o w a less m a r k e d decrease

a n d often a slower recovery. R e c e n t studies o f p l a q u e p H changes b y G . F r o s t e l (2) after ingest i o n o f s o r b i t o l a n d h y d r o g e n a t e d d e x t r i n p r o d u c t s i n d i c a t e that these p r o d u c t s i n d u c e d less p H change t h a n sucrose.

However, Caldwell and


2.

P I G M A N

B i b b y (6)

Carbohydrates,

Fats, Dental

Caries

13

s h o w e d that the p H of carious lesions ( r a t h e r t h a n p l a q u e p H )

i n c r e a s e d w h e n some foodstuffs w e r e taken b y m o u t h . T h e significance of these results i n terms of the r e l a t i o n of h u m a n diets to h u m a n caries experience is u n c e r t a i n . If the a s s u m p t i o n is m a d e that the p r o d u c t i o n of o r g a n i c acids b y o r a l b a c t e r i a is a n i m p o r t a n t feature of the carious process, the results d o p r o v i d e a means f o r d e m o n stration of t h e p o s s i b l e c a r i o g e n i c effects of d i e t a r y c o m p o n e n t s .

How-

ever, as c a r r i e d o u t , the results are at best o n l y s e m i q u a n t i t a t i v e a n d c a p a b l e of d e m o n s t r a t i o n of o n l y gross differences.

They do

suggest,


h o w e v e r , the i n a d v i s a b i l i t y of m a i n t a i n i n g c o n t i n u o u s l y h i g h levels of f e r m e n t a b l e c a r b o h y d r a t e s i n the s a l i v a . In Vitro Caries Production (24).

T h e e n a m e l c o v e r i n g the c r o w n

of h u m a n teeth is w i t h o u t cells a n d is i n c a p a b l e of restoration except b y p u r e l y c h e m i c a l exchange w i t h s a l i v a r y c o m p o n e n t s .

T h e caries process

i n e n a m e l m a y b e r e p r o d u c i b l e b y p u r e l y in vitro p r o c e d u r e s except for s e c o n d a r y effects, s u c h as d e p o s i t i o n of secondary d e n t i n (24).

The many

earlier in vitro experiments b e g u n b y M a g i t o t ( 1 8 7 0 ) a n d other w o r k e r s t e r m i n a t e d i n the d e v e l o p m e n t of the a r t i f i c i a l m o u t h

(24).

T h e o p e r a t i o n of the a r t i f i c i a l m o u t h consists b a s i c a l l y of exposure of m o u n t e d extracted h u m a n teeth to s a l i v a a n d s u b s e q u e n t l y to a bact e r i o l o g i c a l m e d i u m w h i c h m a i n t a i n s the m e t a b o l i s m of the o r a l m i c r o organisms o n the t o o t h surface.

T h e teeth m a y b e b r u s h e d r e g u l a r l y to

s i m u l a t e n a t u r a l lesions, a n d p u r e strains of m i c r o o r g a n i s m s m a y b e u s e d . F o r q u a n t i t a t i v e c o m p a r i s o n s , b l o c k s of h u m a n e n a m e l m a y be

used

i n s t e a d of w h o l e teeth a n d the s o f t e n i n g w h i c h results f r o m the caries

i Journal of the American Dental Association

Figure 2. Pattern of carious attack on lower left second deciduous molar (24) Al, Occlusal aspect; Bl, buccal aspect; CI, mesial aspect; Dl, distal aspect; and El, lingual aspect before the tooth was put on the standard regime. A2, B2, C2, D2 and E2 show the respective surfaces after 9 weeks on the standard regime. y

Copyright by the American Dental Association. Reprinted by permission.


14

DIETARY

C H E M I C A L S

VS.

D E N T A L

p r o d u c t i o n c a n b e f o l l o w e d b y m i c r o h a r d n e s s measurements.

CARIES

Typical

lesions p r o d u c e d i n a b r u s h e d m o l a r a r e s h o w n i n F i g u r e 2. T h e f o l l o w i n g c a r b o h y d r a t e s w e r e tested f o r t h e i r a b i l i t y t o cause the s o f t e n i n g of e n a m e l surfaces i n t h e presence o f o r a l m i c r o o r g a n i s m s : dextrose, fructose, galactose, lactose, maltose, sucrose, a n d s o l u b l e starch. T h e s o l u b l e s t a r c h c a u s e d n o s o f t e n i n g , b u t t h e sugars, w i t h t h e p o s s i b l e exception

of maltose,

showed

comparable

rates

of s o f t e n i n g

(25).

3-O-methyl-D-fructose a n d 3-O-methyl-D-glucose were not fermented b y o r a l m i c r o o r g a n i s m s , b u t 3 - O - m e t h y l - D - g l u c o s e w a s a n e u r o t o x i c agent.


A n interesting relation between

sugar c o n c e n t r a t i o n a n d t h e t y p e

of attack w a s o b s e r v e d w h e n t h e c o n c e n t r a t i o n o f D - g l u c o s e ( d e x t r o s e ) i n t h e b a c t e r i o l o g i c a l m e d i u m w a s s t u d i e d (24).

W i t h sugar a d d e d t o t h e

bacteriological m e d i u m , decalcified dentin was attacked b u t not sound e n a m e l o r d e n t i n ; t h e attack w a s thus p r o t e o l y t i c i n nature.

W i t h 0.5%

dextrose i n t h e m e d i u m , s o u n d e n a m e l a n d d e n t i n w e r e extensively d e c a l c i f i e d , b u t n o attack o n d e c a l c i f i e d d e n t i n w a s o b s e r v e d .

F o r 0.2 to

0 . 3 % solutions, d e n t i n a l m a t r i x w a s a t t a c k e d a n d d e c a l c i f i c a t i o n of s o u n d enamel a n d dentin occurred.

T h e s e results suggest i n terms of h u m a n

o r a l c o n d i t i o n s that t h e c o n c e n t r a t i o n of f e r m e n t a b l e sugar i n t h e s a l i v a w i l l d e t e r m i n e t h e n a t u r e of t h e carious attack, w h i c h m a y v a r y at different times d u r i n g t h e d a y . T h e a r t i f i c i a l m o u t h has b e e n u s e d f o r tests o f t h e c a r i o g e n i c i t y of foodstuffs. K o u l o u r i d e s ( u n p u b l i s h e d d a t a ) s u s p e n d e d breakfast cereals ( c o r n b a s e ) i n w a t e r a n d u s e d this as t h e b a c t e r i o l o g i c a l m e d i u m . T h e p r i n c i p a l q u e s t i o n w i t h r e g a r d t o this p r o c e d u r e is w h e t h e r t h e m i c r o b i a l p o p u l a t i o n is t r u l y representative of t h e r e a l flora of t h e o r a l c a v i t y . T h e attack rate is c o n s i d e r a b l y faster t h a n that u s u a l l y o b s e r v e d in the h u m a n mouth. Oral Clearance Studies and Food Retention C l i n i c a l dentists g e n e r a l l y h a v e associated caries lesions w i t h n o n c l e a n s i n g areas of teeth a n d the r e s u l t i n g a c c u m u l a t i o n of f o o d p a r t i c l e s . S u c h areas also w o u l d t e n d t o f a v o r f o r m a t i o n of b a c t e r i a l p l a q u e s . recent years, m a n y l a b o r a t o r y investigations i n t o t h e factors

In

affecting

t h e rate of r e m o v a l of f o o d p r o d u c t s f r o m t h e m o u t h h a v e b e e n c a r r i e d out. T h e s e h a v e b e e n r e v i e w e d b y V o l k e r a n d C a l d w e l l (35).

T h e prin-

c i p a l studies h a v e b e e n c a r r i e d o u t b y d i r e c t measurements of t h e a m o u n t of f o o d residues after v a r i o u s times o f c h e w i n g , b y measurements o f t h e a m o u n t of s a l i v a r y r e d u c i n g sugar d u r i n g a n d after d i g e s t i o n of f o o d , a n d b y measurements o f p r o p e r t i e s of foods ( s u c h as a d h e s i o n ) w h i c h w o u l d b e e x p e c t e d t o affect f o o d r e t e n t i o n .


2.

Carbohydrates,

P I G M A N

Bibby

a n d associates

Fats, Dental (35)

have

15

Caries

s t u d i e d the

retention

of

food

p a r t i c l e s i n the m o u t h d u r i n g c h e w i n g a n d h a v e c o m p a r e d v a r i o u s f o o d p r o d u c t s . T h e y also m e a s u r e d the a c i d f o r m e d b y the f o o d s w h e n i n c u bated w i t h saliva, a n d established a "Decalcification Potential" based o n b o t h measurements.

F i g cookies, dates, chocolates, a n d i c e c r e a m w e r e

r e t a i n e d i n h i g h e s t a m o u n t s , a n d p o t a t o c h i p s a n d carrots ( c o o k e d a n d u n c o o k e d ) w e r e c l e a r e d the most r a p i d l y of the foods s t u d i e d . C a l d w e l l (5, 35)

d e v e l o p e d a n a p p a r a t u s to m e a s u r e the a d h e s i o n

o f f o o d p r o d u c t s to t o o t h e n a m e l in vitro.

T h e results f o r a w i d e r a n g e


of foods s h o w e d t h a t the foods h a d m a r k e d l y different a d h e s i v e p r o p e r ties. C a r a m e l s a n d toffe ( a h a r d c a n d y ) w e r e the most a d h e s i v e f o o d s . V o l k e r a n d P i n k e r t o n ( 1 9 4 7 ) first u s e d s a l i v a r y r e d u c i n g sugar as a m e a s u r e of f o o d r e t e n t i o n b y h u m a n subjects b y L u n d q v i s t (20)

(33).

It w a s u s e d also

as p a r t of the c o m p r e h e n s i v e V i p e h o l m s t u d y

a n d later b y L a n k e (18)

(32)

i n a n extension of the V i p e h o l m s t u d y t o o r a l

c l e a r a n c e studies of foods. T a b l e I I f r o m V o l k e r ( 3 3 ) , shows t h e s a l i v a r y r e d u c i n g sugar levels after i n g e s t i o n of several foodstuffs.

Table II. Reducing Sugar (as D-Glucose) in H u m a n Saliva" after Ingestion of Several Foods or Confections b

. . Time of Eating, Min. rT1

Substance Chewing gum, D e n t y n e , 3.2 grams Soft m i n t , B i r c h B i t , 2.5 g r a m s Hard mint, Toronto M i n t , 1.9 g r a m s Chewy candy, C h o c l e t t o , 5.9 grams Cookie, vanilla wafer, 8.2 g r a m s Bread and jam, 76.0 g r a m s

No. of Subjects

Av. Glucose Cone, in ma. 0 Time

c

5 Min.

d

15 Min.

d

% 30 Min*

28

30 (chewing)

19

484

147

26

12

4

16

662

131

23

12

9 (av.)

21

377

259

24

11

7

24*

1,909

269

26

12

2.5

16

889

117

18

12

3

25

1,475

149

22

" Reducing substances in saliva calculated as glucose. From Volker (33). Copyright by the American Dental Association. Reprinted by permission. Zero time value is control value taken immediately before beginning the ingestion of the test substances. Time intervening since the beginning of ingestion of the test substances. 6

c

d


16

DIETARY

C H E M I C A L S

VS.

D E N T A L

CARIES

The Vipeholm Dental Caries Study T h e V i p e h o l m D e n t a l C a r i e s S t u d y w a s c e r t a i n l y t h e best d e s i g n e d a n d c o n d u c t e d a n d t h e freest of c r i t i c i s m o f a l l c l i n i c a l studies o f t h e d i r e c t effect of foodstuffs o n caries i n c i d e n c e i n h u m a n s . I n s t i t u t i o n a l i z e d m e n t a l patients principally.

( 4 3 6 ) u n d e r close s u p e r v i s i o n a n d c o n t r o l w e r e u s e d

T w o studies, e a c h of 2 years' d u r a t i o n , f o l l o w e d 2 years of

p r e p a r a t i o n a n d p r e l i m i n a r y studies. S e v e n groups w e r e f o r m e d , a l l w i t h a basic diet plus supplements:


( 1 ) C o n t r o l G r o u p o n basic d i e t w i t h 150 grams o r 4 0 grams of m a r g a r i n e as c a l o r i c c o m p e n s a t i o n f o r c a r b o h y d r a t e s a d d e d i n other diets. (2)

Sucrose G r o u p g i v e n sucrose i n s o l u t i o n at meals.

(3)

B r e a d G r o u p g i v e n s u g a r - r i c h b r e a d o r rolls.

( 4 ) C h o c o l a t e G r o u p g i v e n sucrose i n s o l u t i o n f o r first 2 years a n d m i l k chocolate f o r t h e last 2 years. ( 5 ) C a r a m e l G r o u p g i v e n s u g a r - r i c h b r e a d t h e first year, caramels the next 2 years, a n d n o s u p p l e m e n t t h e last year. ( 6 ) 8-Toffee G r o u p g i v e n n o s u p p l e m e n t t h e first year a n d 8 toffees ( h a r d c a n d i e s ) d a i l y f o r 3 years. ( 7 ) 24-Toffee G r o u p g i v e n 24 toffees d a i l y f o r 1.5 years a n d n o s u p p l e m e n t f o r t h e last 2.5 years. T h e basic d i e t f o r t h e first 2 years w a s 1800 calories, l o w i n sugars b u t h a v i n g c o n s i d e r a b l e b r e a d a n d potatoes

as c a r b o h y d r a t e

sources.

T h e b a s i c d i e t f o r t h e last 2 years p r o v i d e d 2700 calories, a n d t h e a m o u n t s of b r e a d a n d potatoes w e r e i n c r e a s e d p a r t i c u l a r l y . T h e v i t a m i n a n d m i n e r a l content w e r e s t u d i e d a n d c o n s i d e r e d satisfactory. C a n d i e s , w h e n g i v e n i n a d d i t i o n to t h e basic diet, a p p a r e n t l y c o u l d b e eaten

between

meals. T h e c a r b o h y d r a t e c o n s u m p t i o n b y groups w a s r e c o r d e d . C a r e f u l d e n t a l examinations w e r e c a r r i e d o u t a n n u a l l y , w i t h t w o examinations p r i o r to the s t u d y . Some of the results are as f o l l o w s . W h e n t h e sugar w a s c o n s u m e d o n l y at meals a n d t h e t o t a l a m o u n t c o n s u m e d w a s c o m p a r e d w i t h d e n t a l caries experiences, p r a c t i c a l l y n o r e l a t i o n c o u l d b e d e m o n s t r a t e d , a n d the caries rate w a s l o w . W h e n t h e candies w e r e g i v e n b e t w e e n meals, a m a r k e d e n h a n c e m e n t of rate w a s d e m o n s t r a t e d o v e r t h e c o n t r o l g r o u p . W h e n t h e candies w e r e r e m o v e d , t h e rates d r o p p e d a g a i n i n t h e subsequent period. T h e conclusions of t h e s t u d y a r e : (1)

T h e c o n s u m p t i o n of sugar c a n increase caries a c t i v i t y .

( 2 ) T h e risk of sugar i n c r e a s i n g caries a c t i v i t y is great i f t h e sugar is c o n s u m e d i n a f o r m w i t h a strong t e n d e n c y to b e r e t a i n e d o n t h e surface o f t h e teeth. ( 3 ) T h e risk of sugar i n c r e a s i n g caries a c t i v i t y is greatest i f t h e sugar is c o n s u m e d b e t w e e n meals a n d i n a f o r m i n w h i c h t h e t e n d e n c y to b e


2.

P I G M A N

Carbohydrates,

Fats, Dental

Caries

17

r e t a i n e d o n t h e surface of t h e t e e t h is p r o n o u n c e d , w i t h a t r a n s i e n t l y h i g h c o n c e n t r a t i o n of sugar o n these surfaces. ( 4 ) T h e increase i n caries a c t i v i t y u n d e r u n i f o r m e x p e r i m e n t a l c o n d i t i o n s varies w i d e l y f r o m one p e r s o n to another. ( 5 ) Increase i n caries a c t i v i t y d u e to intake o f s u g a r - r i c h foodstuffs c o n s u m e d i n a m a n n e r f a v o r i n g caries d i s a p p e a r s o n w i t h d r a w a l of s u c h foodstuffs f r o m t h e d i e t . ( 6 ) C a r i e s lesions m a y c o n t i n u e to a p p e a r despite the a v o i d a n c e of r e f i n e d sugar a n d m a x i m u m r e s t r i c t i o n o f n a t u r a l sugars a n d t o t a l d i e t a r y carbohydrates. Downloaded by CORNELL UNIV on August 23, 2016 | http://pubs.acs.org Publication Date: June 1, 1970 | doi: 10.1021/ba-1970-0094.ch002

B y sugar, sucrose w a s meant, a n d t h e s t u d y seemed to evaluate p r i m a r i l y the effects of candies t a k e n b e t w e e n meals. Sugars t a k e n n o r m a l l y at meals h a d l i t t l e influence. S t a r c h p r o d u c t s w e r e n o t c o n s i d e r e d . T h e significance o f t h e s t u d y w a s c o n s i d e r a b l y e n h a n c e d b y a p a r a l l e l s t u d y b y L u n d q v i s t (20)

of t h e same g r o u p s . F o r this s t u d y , t h e s a l i v a r y

r e d u c i n g sugars ( a f t e r a c i d h y d r o l y s i s of s a l i v a s a m p l e s ) w e r e m e a s u r e d at 15-minute p e r i o d s d u r i n g t h e w o r k i n g hours o n t y p i c a l days f o r the seven g r o u p s . T h e s e studies s h o w e d increases b e t w e e n meals, a n d w i t h some persons the salivas almost c o n t i n u o u s l y h a d glucose e q u i v a l e n t s o f 0.3 to 2 % . T h e s a l i v a r y r e d u c i n g sugar profiles f o r t h e v a r i o u s g r o u p s are s h o w n i n F i g u r e 3. T h e figure also gives t h e caries a c t i v i t y o f t h e g r o u p s . T h e i n d i v i d u a l patterns of s a l i v a r y r e d u c i n g sugar w e r e q u a n t i t a t e d b y c a l c u l a t i o n of a clearance t i m e b a s e d o n the r e d u c i n g sugar c o n c e n t r a t i o n a n d percentage of the w a k i n g hours i n v o l v e d .

These

clearance

times f o r the v a r i o u s groups c o r r e l a t e d closely w i t h the caries a c t i v i t y , as s h o w n i n F i g u r e 4. I n a separate s t u d y u s i n g t w o persons, L u n d q v i s t (20,35)

also m e a -

s u r e d the clearance o f a large n u m b e r o f foods b y m e a s u r i n g the s a l i v a r y r e d u c i n g sugar ( a f t e r a c i d h y d r o l y s i s ) o v e r a p e r i o d of t i m e . T h e results d i d n o t correlate a l w a y s w i t h the t o t a l c a r b o h y d r a t e content, a l t h o u g h candies a n d s u g a r - r i c h p r o d u c t s w e r e g i v e n the highest caries p o t e n t i a l i t y index. A l t h o u g h the p h y s i c a l consistency of foods g e n e r a l l y has b e e n r e l a t e d to c a r b o h y d r a t e o r a l clearance, recent w o r k has i n d i c a t e d that the e l i m i n a t i o n of s o l i d foods f r o m diets of rodents r e s u l t e d i n a r a p i d decrease of s a l i v a r y g l a n d f u n c t i o n a n d g l a n d w e i g h t (14).

I n a d d i t i o n to f o o d

clearance a n d s a l i v a r y g l a n d a t r o p h y , a t h i r d factor has b e e n suggested as c o n t r i b u t i n g to h i g h e r t o o t h resistance

against caries.

T h i s is t h e

m e c h a n i c a l effect of m a s t i c a t i o n o n the crystallites of t h e e n a m e l structure (21).

A l t h o u g h d i r e c t e v i d e n c e f o r this factor is l a c k i n g , it m a y b e a n

a d d i t i o n a l m e c h a n i s m r e l a t i n g t h e p h y s i c a l consistency of foods to the d e v e l o p m e n t of d e n t a l caries.


18

C H E M I C A L S

VS.

D E N T A L

CARIES


DIETARY

Ttaw of day Odontologisk Revy

Figure 3. Concentrations of salivary reducing sugar during the waking periods of persons in the seven groups of the Vipeholm Study as given by Lundqvist (20)

The Place of Sucrose Sucrose is one o f the most i m p o r t a n t i n d u s t r i a l sugars u s e d i n foods. A l t h o u g h most of t h e early studies c i t e d p r e v i o u s l y d i d n o t differentiate sucrose f r o m other c o m m e r c i a l sugars a n d starches, c o n s i d e r a b l e recent w o r k suggests that i t m a y b e m o r e c a r i o g e n i c . T h i s recent w o r k has b e e n


2.

P I G M A N

Carbohydrates,

Fats, Dental

Caries

19

r e v i e w e d b y N e w b r u n ( 2 2 ) . T h e basis f o r t h e s p e c i a l effect is t h e r e l a tionship of the cariogenicity of streptococci

a n d some

other m i c r o -

organisms t o t h e i r a b i l i t y t o f o r m b a c t e r i a l p l a q u e s a n d e x t r a c e l l u l a r dextrans a n d levans. E x p e r i m e n t a l l y , these p o l y s a c c h a r i d e s a r e f o r m e d f r o m sucrose b u t n o t f r o m glucose o r other c o m m o n sugars. T h e s e p o l y saccharides a p p a r e n t l y a i d p l a q u e g r o w t h b y h e l p i n g t h e m i c r o o r g a n i s m s to a t t a c h themselves to t h e e n a m e l surface. T h e y m a y act also as a storage f o r m o f fructose o r glucose w h i c h m a y b e released s l o w l y b e t w e e n meals. G u s t a f s o n et al. (12) e a r l y s h o w e d that t h e caries a c t i v i t y o f e x p e r i -


m e n t a l diets f o r hamsters w a s r e l a t e d t o t h e sucrose content. (17)

Krasse

f o u n d that sucrose w a s better t h a n glucose i n i n d u c i n g p l a q u e s o f

c a r i e s - i n d u c i n g streptococci.

T h e i n c l u s i o n o f sucrose i n a n i m a l diets

c a u s e d the p r o d u c t i o n o f b o t h e x t r a c e l l u l a r a n d i n t r a c e l l u l a r p o l y s a c c h a rides, w h e r e a s glucose c a u s e d t h e f o r m a t i o n o f o n l y i n t r a c e l l u l a r m a t e r i a l (9). Rats o r hamsters w h i c h h a d t h e i r i n d i g e n o u s o r a l flora depressed b y the use o f a n t i b i o t i c s w e r e i n o c u l a t e d w i t h c a r i o g e n i c streptococci.

Diets

c o n t a i n i n g 2 5 % o f t h e f o l l o w i n g c a r b o h y d r a t e s w e r e u s e d : sucrose, g l u cose, fructose, maltose, a n d u n c o o k e d starch.

T h e streptococci d i d not

s u r v i v e i n a n i m a l s f e d o n diets l a c k i n g i n sucrose, a n d t h e highest caries experience w a s f o u n d f o r t h e g r o u p g i v e n sucrose (8, 11). I n other s i m i l a r studies, b u t w i t h n a t u r a l o r a l flora, o n rats f e d diets i n w h i c h a n u m b e r o f c a r b o h y d r a t e s w e r e c o m p a r e d w i t h sucrose, t h e results w e r e m o r e e q u i v o c a l . A l l o f t h e sugars p r o d u c e d c o m p a r a b l e caries, at least i n some experiments (10, 26, 27). W i t h m o n k e y s o n c a r b o h y d r a t e - r e s t r i c t e d diets, B o w e n a n d C o r n i c k (3)

f o u n d that the o r a l p o p u l a t i o n o f b a c t e r i a w h i c h f o r m e d p o l y s a c c h a -

rides decreased a n d i n c r e a s e d w h e n c a r b o h y d r a t e s w e r e i n c o r p o r a t e d into t h e diets.

Bread

Control Sucrose Chocolate 8 Toffee Caramel 24 Toffee Odontologisk Revy

Figure 4. Comparison of clearance of reducing sugar from the saliva of persons in the Vipeholm Study (Lundqvist, 20)


20

DIETARY

C H E M I C A L S

VS.

D E N T A L

CARIES

Present Status Basis of Variability of Caries Experience. O n e of the c o n c l u s i o n s of the V i p e h o l m s t u d y w a s that despite a stringent c o n t r o l of the h u m a n e x p e r i m e n t a l subjects, c o n s i d e r a b l e

v a r i a t i o n i n caries

experience

c u r r e d i n e a c h g r o u p . T h i s agrees w i t h g e n e r a l c l i n i c a l experience

ocof

great v a r i a t i o n s b e t w e e n i n d i v i d u a l s (e.g., f a m i l y g r o u p s ) w i t h s i m i l a r environments.

It is also of interest that a b o u t one or t w o persons

per

t h o u s a n d are c o m p l e t e l y caries-free at the age of n a v a l recruits. T h i s v a r i a b i l i t y suggests that at best the r e l a t i o n s h i p b e t w e e n d e n t a l Downloaded by CORNELL UNIV on August 23, 2016 | http://pubs.acs.org Publication Date: June 1, 1970 | doi: 10.1021/ba-1970-0094.ch002

caries experience a n d d i e t a r y factors is not a s i m p l e cause-effect r e l a t i o n , a l t h o u g h m u c h e v i d e n c e exists that m a n y c a r b o h y d r a t e s c a n b e c o n s i d e r e d as c a r i o g e n i c u n d e r some c o n d i t i o n s . T h e v a r i a b i l i t y p r e s u m a b l y arises f r o m a n u m b e r of factors, some of w h i c h c a n b e classified as h e r e d i t a r y factors. T h e most o b v i o u s h e r e d i t a r y factors are the size, shape, a n d arrangem e n t of teeth i n the m o u t h , the a m o u n t a n d c o m p o s i t i o n of the s a l i v a , a n d the r e l a t i o n of the soft tissues to the teeth. w o u l d b e r e l a t e d to self-cleansing

M o s t of these factors

a n d food retention

characteristics,

a l t h o u g h s a l i v a r y effects c o u l d be e v e n m o r e p r o f o u n d a n d i n v o l v e s u c h components

as buffers,

antibacterial

agents, a n d e n a m e l

rehardening

materials. V a r i a b i l i t y not r e l a t e d to genetic factors also c o u l d arise f r o m d i f ferences a n d changes i n the o r a l m i c r o f l o r a .

T h i s factor r e c e n t l y

r e c e i v e d c o n s i d e r a b l e interest i n the w o r k of K e y e s et al.

(29).

has The

m a t u r a t i o n of t o o t h surfaces after e r u p t i o n is another source of v a r i a t i o n , one of the most c r i t i c a l k n o w n factors b e i n g exposure to fluorides i n the d i e t or w a t e r . Controllable Factors. T h e a b o v e causes of v a r i a b i l i t y ( e x c e p t ride)

are

essentially

innate a n d not subject to d i e t a r y c o n t r o l .

p r o b l e m that remains is to d e t e r m i n e h o w to m i n i m i z e the c a r i o g e n i c effects of most d i e t a r y c a r b o h y d r a t e s .

fluThe

potential

G e n e r a l l y , the p r o b l e m

seems to r e d u c e itself to d e t e r m i n i n g h o w foodstuffs c a n b e k e p t f r o m contact or b e r e m o v e d f r o m the teeth a n d o r a l c a v i t y as r a p i d l y as possible. Sufficient e v i d e n c e n o w exists to s h o w that s t i c k y c a r b o h y d r a t e - r i c h foods s h o u l d be r e m o v e d f r o m the h u m a n diet as m u c h as

possible.

T h i s a c t i o n w i l l r e q u i r e the l i s t i n g of specific items after c a r e f u l c o n s i d e r a t i o n of the e v i d e n c e . h e a l t h agencies.

P r e s u m a b l y , this s h o u l d b e d o n e b y a p p r o v e d

T h e r e s t r i c t i o n of c a r i o g e n i c substances to

mealtimes

also requires emphasis. T h e same c a r b o h y d r a t e i n different p h y s i c a l f o r m s m a y v a r y m a r k e d l y i n c a r i e s - p r o d u c i n g a c t i v i t y . T h i s s i t u a t i o n suggests that

manufac-

turers of foodstuffs c o n s i d e r the r e l a t i o n to p o t e n t i a l c a r i o g e n i c i t y i n


2.

PiGMAN

Carbohydrates, Fats, Dental Canes

21

their formulation and processing methods. In general, methods are probably available for making this judgment. Thus, Volker (33) made a preliminary study of an Army F i e l d Ration and showed slow oral clearance.


In some instances, it may be possible also to substitute a less cariogenic for a more cariogenic component. Mixtures often are used widely in processed foods, but the judgment is mainly on taste and consistency, and not on cariogenicity. A n alternative, possible in some applications, would be to incorporate cariostatic agents. The accumulated scientific knowledge is currently such that the cariogenicity of carbohydrate products can be evaluated reasonably well. W e now should be able to terminate the period in which most of the dental profession condemned carbohydrates of all types in all applica tions, and the food industry as a whole responded by refusals to consider the possible cariogenicity of its products. B y cooperation of dental and health agencies with a receptive industry, dental caries experience can be reduced greatly. Acknowledgment The preparation of this section was supported by a grant from the American Chicle Co., Division of Warner-Lambert Pharmaceutical Co. I also express my thanks to J. M . Navia for help in revising this manu script. Literature Cited (1) Bibby, B. G., Shaw, J. H., Intern. Dental J. 1965, 15, 1. (2) Blix, G. (Ed.), "Nutrition and Caries Prevention," Swedish Nutrition Foundation, Almqvist and Wiskells, Uppsala, 1965. (3) Bowen, W. H . , Cornick, D . E., Helv. Odontol. Acta 1967, 11, 27. (4) Brislin, J. F., Cox, G. J., "Survey of the Literature of Dental Caries," Univ. of Pittsburgh Press, Pittsburgh, Pa., 1964. (5) Caldwell, R. C., J. Dental Res. 1962, 41, 821. (6) Caldwell, R. C., Bibby, B. G., J. Dental Assoc. 1958, 57, 685. (7) Csaky, T. Z., Ann. Ν. Y. Acad. Sci. 1965, 131, 868. (8) Frostell, G., Keyes, P. H., Larson, R. H., J. Nutr. 1967, 93, 65. (9) Gibbons, R. J., Socransky, S. S., Arch. Oral Biol. 1962, 7, 73. (10) Green, R. M . , Hartles, R. L., Arch. Oral Biol. 1969, 14, 235. (11) Guggenheim, B., Konig, K. G., Herzog, E., Muhlemann, H . R., Helv. Odontol. Acta 1966, 10, 101. (12) Gustafson, G., Stellings, E., Abramson, E., Brumius, E., Odontol. Tidskr. 1953, 61, 386. (13) Haldi, J., Law, M. L., John, J., J. Dental Res. 1967, 46, 739. (14) Hall, H . D., Schneyer, C. Α., Proc. Soc. Exptl. Biol. Med. 1964, 117, 789. (15) Halloway, P. J., Shaw, J. H . , Sweeney, J., Arch. Oral Biol. 1961, 3, 185. (16) Koulourides, T., Alabama Dental Rev. 1963, 11, 10. (17) Krasse, B., Arch. Oral Biol. 1965, 10, 215, 223. (18) Lanke, L. S., Acta Odontol. Scand. 1957, 15, Suppl. 23.


22 (19) (20) (21) (22) (23) (24) (25) (26) (27) (28)


(29) (30) (31) (32) (33) (34) (35)

DIETARY CHEMICALS VS. DENTAL CARIES

Larson, R. H . , J. Am. Dietet. Assoc. 1964, 44, 368. Lundqvist, C., Odontol. Rev. 1952, 3, Suppl. 1. Neumann, H . H . , DiSalvo, N. A., Ann. N. Y. Acad. Sci. 1965, 131, 893. Newbrun, E., J. Dentistry Children 1969, 36, 239. Pigman, W., "The Carbohydrates," p. 807, Academic Press, New York, 1957. Pigman, W., J. Am. Dental Assoc. 1955, 51, 685. Pigman, W., Brasher, J., Koulourides, T., Nature 1962, 195, 190. Shaw, J. H . , Griffiths, D., J. Nutr. 1963, 80, 123. Shaw, J. H . , Krumins, I., Gibbons, R. J., Arch. Oral Biol. 1967, 12, 755. Sognnaes, R. F., Ed., "Advances in Experimental Caries Research," American Association for the Advancement of Science, Washington, D . C., 1955. Sognnaes, R. F., Ed., "Chemistry and Prevention of Dental Caries," Thomas, Springfield, Ill., 1962. Sognnaes, R. F., J. Am. Dental Assoc. 1948, 37, 676. Stephan, R. M., J. Dental Res. 1966, 45, 1551. Vipeholm Dental Caries Study, Acta Odontol. Scand. 1954, 11, 195-388. Volker, J. F., J. Am. Dental Assoc. 1955, 51, 285. Volker, J. F., " A Symposium on Preventive Dentistry," M . K. Hine, J. C. Muhler, Eds., Mosby, St. Louis, Mo., 1956. Volker, J. F., Caldwell, R. C., "Clinical Pedodontics," S. F. Finn, Ed., Saunders, Philadelphia, Pa., 1967.

RECEIVED August 14,

1968.


Dietary Chemicals vs. Dental Caries

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