Dietary Chemicals vs. Dental Caries - ACS Publications

9

Effect of Minerals on Dental Caries

J U A N M . NAVIA

1

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Massachusetts Institute of Technology, Cambridge, Mass.

Minerals in foods and drinking water have an important role in dental caries. Trace elements can be incorporated preeruptively and posteruptively into tooth enamel and change its physicochemical properties, affect the remineralization processes on the enamel surface, and influence the implantation and metabolism of cariogenic microorganism. Some elements promote caries, such as Se, Mg, and Cd, while others, such as Mo, V, and Sr, are mildly cariostatic. The effect of many other elements on caries is not known clearly owing to experimental limitations of the animal models used to study them. The species of animals used, the type of oral flora, the toxicity effects, and the interrelations between elements have to be evaluated and defined before a clear understanding of the role of trace elements in human caries is achieved.

The

concept that nutritional deficiencies are related to infection has been documented amply in the literature (166). Attempts to show through epidemiological studies that optimum nutrition inhibits dental caries, an infectious oral disease, have been unsuccessful (157). Caries prevalence is markedly lower in more isolated or primitive areas where the nutritional status is definitely poorer than in sections of the country with access to technical developments characteristic of modern civilization (156). This observation was voiced 30 years ago when Brekhus and Armstrong (21) stated that dental caries is a disease of civilization and that freedom from caries, found in societies less technically advanced, results from other factors besides nutrition. Dental decay is increasing among 1

Present address: Institute of Dental Research, University of Alabama in Birmingham, Birmingham, Ala. 35233. 123 In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

124

DIETARY

C H E M I C A L S

VS.

D E N T A L

t e c h n i c a l l y d e v e l o p i n g nations a n d is r a p i d l y a p p r o a c h i n g the levels f o u n d i n affluent societies.

A r e p o r t b y B a u m e (12)

CARIES

severity

describes t h e

d e n t a l a n d n u t r i t i o n a l status of the s c h o o l p o p u l a t i o n of F r e n c h P o l y n e s i a a n d illustrates the p o i n t .

The

w o r s t d e n t a l c o n d i t i o n s of the

t e r r i t o r y w e r e f o u n d i n the d e v e l o p i n g d i s t r i c t of Papeete.

entire

A m o n g the

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

caries

p r e v a i l e d , p a r t i c u l a r l y a m o n g those of C h i n e s e extraction. A l m o s t i m m e d i a t e l y after e r u p t i o n of " y e l l o w " p e r m a n e n t teeth, a smooth-surface t y p e of caries " m e l t e d d o w n " these h y p o p l a s t i c teeth so that at age 13 to 15 Downloaded by UNIV OF PITTSBURGH on May 4, 2015 | http://pubs.acs.org Publication Date: June 1, 1970 | doi: 10.1021/ba-1970-0094.ch009

years the T a h i t i a n s are p r a c t i c a l l y edentulous. T h e teeth of youngsters r a i s e d o n a deficient d i e t are n o t a b l e to w i t h s t a n d the i m p a c t of the c a r i e s - p r o m o t i n g d i e t c o n s u m e d i n u r b a n locations w h i l e the i n h a b i t a n t s of distant i s l a n d s , w h o s t i l l a d h e r e

to

their traditional food habits, maintain good dental health. T h e change i n dietary habits

associated

with

technical

and

economic

development

p r o b a b l y is r e s p o n s i b l e f o r this d e t e r i o r a t i o n i n d e n t a l h e a l t h w h i c h m a y b r i n g r a m p a n t disease to some p o p u l a t i o n groups w i t h i n a generation. O n e factor that has i n t e r f e r e d w i t h efforts to u n d e r s t a n d the nature a n d extent of the i n t e r a c t i o n b e t w e e n n u t r i t i o n a n d d e n t a l caries is the diverse effect of nutrients ( a n d n o n n u t r i e n t s ) i n the d i e t d u r i n g the pree m p t i v e a n d p o s t - e r u p t i v e p e r i o d s of t o o t h d e v e l o p m e n t .

Pre-emptively,

nutrients i n the d i e t c a n influence the m a t u r a t i o n process, the c h e m i c a l c o m p o s i t i o n of teeth, t o o t h size a n d m o r p h o l o g y a n d , to a lesser extent, the t i m e of e m p t i o n . N u t r i e n t s i n the diet also c a n select o u t the c a r i o g e n i c flora b y the process of e n r i c h m e n t a n d thus f a c i l i t a t e the i m p l a n t a t i o n a n d c o l o n i z a t i o n of these m i c r o o r g a n i s m s o n the t o o t h surface once it has e m p t e d i n t o the o r a l e n v i r o n m e n t .

Post-emptively, diet can influ-

ence p l a q u e f o r m a t i o n a n d the m i c r o b i a l m e t a b o l i c a c t i v i t y i n the m i c r o e n v i r o n m e n t of teeth, the c o m p o s i t i o n of s a l i v a b a t h i n g the teeth, a n d the c o m p o s i t i o n of the e n a m e l surface.

T h e pre-emptive a n d post-erup-

t i v e effects of d i e t o n the d e v e l o p m e n t a n d m a i n t e n a n c e

of teeth h a v e

not a l w a y s b e e n c l e a r l y separted i n e x p e r i m e n t a l designs a n d h a v e c o n f u s e d the i n t e r p r e t a t i o n of some results. W h i l e most nutrients m a y h a v e t h e i r major effect o n d e n t a l structures p r e - e m p t i v e l y d u r i n g the process of g r o w t h a n d d e v e l o p m e n t , m i n e r a l s h a v e a p r o f o u n d influence p r e - e m p t i v e l y a n d p o s t - e m p t i v e l y a n d , therefore, p l a y a m a j o r r o l e i n the caries s u s c e p t i b i l i t y or resistance of the t o o t h . T h e i n o r g a n i c p o r t i o n of p r o t e c t i v e foods w i l l c o n t r i b u t e p r a c t i c a l l y a l l of the caries-protective a c t i o n of the f o o d

(14).

F r o m the s t a n d p o i n t of n u t r i t i o n , m i n e r a l elements are either essent i a l f o r the m a i n t e n a n c e

of l i f e processes o r nonessential.

B e c a u s e of

their u b i q u i t o u s n e s s , t h e y m a y enter the tissues i n a n a d v e n t i t i o u s m a n ner w h e n present i n the f o o d a n d w a t e r c o n s u m e d or i n the a i r i n h a l e d .

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

9.

NAVIA

Effect of

125

Minerals

T h e m i n e r a l s present i n a n i m a l tissues c a n b e a r b i t r a r i l y d i v i d e d i n t o m a j o r elements o r m a c r o m i n e r a l s , s u c h as C a , P , M g , N a , K , S, a n d C I , a n d trace elements o r m i c r o m i n e r a l s , s u c h as C u , C o , F e , I, M n , M o , Se, a n d Z n , w h i c h are k n o w n t o d a y as t h e e i g h t essential elements.

Another

g r o u p of trace elements w h i c h i n c l u d e s A l , A s , B , B a , B e , F , H g , N i , R b , S i , S r , a n d V m a y b e present, b u t as y e t n o specific f u n c t i o n has b e e n a t t a c h e d to t h e m .

S o m e elements s u c h as V a n d Sr p o s s i b l y m a y b e

s h o w n essential i n f u t u r e investigations. T h e major m i n e r a l elements i n t h e a n i m a l b o d y are d e p o s i t e d i n Downloaded by UNIV OF PITTSBURGH on May 4, 2015 | http://pubs.acs.org Publication Date: June 1, 1970 | doi: 10.1021/ba-1970-0094.ch009

b o n e a n d teeth, w h e r e t h e y either increase t h e r i g i d i t y of bones o r serve as storage f o r use b y tissue cells w h e n necessary i n o r d e r to m a i n t a i n t h e i n t e g r i t y of m e t a b o l i c f u n c t i o n s . T r a c e elements m a y enter e n z y m e reactions as activators w h i c h b r i n g t h e e n z y m e into a c a t a l y t i c a l l y active state. E n z y m e a c t i v i t y is affected b y t h e presence o r absence of m i n e r a l salts, t h e n a t u r e of t h e ions present, a n d t h e i r concentrations.

Certain

elements s u c h as Z n , C u , a n d M o are essential s t r u c t u r a l c o m p o n e n t s of e n z y m e s s u c h as c a r b o n i c a n h y d r a s e , p o l y p h e n o l oxidase, a n d x a n t h i n e oxidase, r e s p e c t i v e l y , w h i l e others l i k e A g , H g , a n d P b m a y b e h i g h l y inhibitory to enzymes. T h e r e q u i r e m e n t s of a n i m a l organisms f o r trace elements is u n k n o w n to a large extent. T h e y are present i n tissues at e x t r e m e l y l o w c o n c e n t r a tions, a n d because i n t h e i r m e t a b o l i c a c t i v i t y t h e y are r e c y c l e d a n d p o o r l y excreted, t h e i r r e - u t i l i z a t i o n b y t h e tissues is n e a r l y c o m p l e t e .

Examples

of these cycles are t h e m e t a b o l i c r e - u t i l i z a t i o n of i r o n a n d i o d i n e . O n l y i n p e r i o d s of n u t r i t i o n a l stress o r i n c r e a s e d m e t a b o l i c a c t i v i t y s u c h as g r o w t h a n d d e v e l o p m e n t , p r e g n a n c y , o r l a c t a t i o n is t h e r e q u i r e m e n t of these elements increased. E v e n i n these c i r c u m s t a n c e s , t h e b i o l o g i c a l reserves i n organs s u c h as t h e l i v e r o r bones u s u a l l y are sufficient to offset a n u t r i t i o n a l d e f i c i e n c y . T h e w h o l e subject of trace element r e q u i r e m e n t s is i n great n e e d of a serious, d e d i c a t e d e x p e r i m e n t a l s t u d y . T h e t h e o r y that t h e m i n e r a l p o r t i o n s of foods c a n affect d e n t a l caries has b e e n s u b s t a n t i a t e d b y " n a t u r a l " g e o g r a p h i c experiments w h e r e a h i g h o r l o w i n c i d e n c e of caries i n h u m a n s appears to b e associated w i t h a d e f i c i e n c y o r excess of a c e r t a i n element i n t h e s o i l a n d p l a n t s g r o w n i n a l o c a l i t y a n d a n i m a l caries experiments.

Geographic Variations in Caries and Trace Elements. w o r k e r s {2,3)

A d l e r a n d co-

h a v e r e p o r t e d o n t h e influence of m o l y b d e n u m o n d e n t a l

caries i n H u n g a r y . T h e y s h o w e d that i n areas w h e r e t h e M o l e v e l i n the w a t e r w a s 0.1 p p m there w a s a l o w i n c i d e n c e of caries. I n 1955, H e w a t a n d E a s t c o t t ( 8 5 ) suggested that a p o s s i b l e c o r r e l a t i o n exists b e t w e e n caries i n c i d e n c e a n d soil c o m p o s i t i o n i n N e w Z e a l a n d . I n o r d e r to s t u d y this subject f u r t h e r , L u d w i g et ah (107)

compared the


126

D I E T A R Y

C H E M I C A L S

VS.

D E N T A L

caries i n c i d e n c e of t w o p o p u l a t i o n s of c h i l d r e n i n t w o adjacent

CARIES

cities

( N a p i e r a n d H a s t i n g s ) . T h e y f o u n d that the N a p i e r c h i l d r e n h a d c o n s i d e r a b l y less caries t h a n the H a s t i n g s c h i l d r e n of c o m p a r a b l e age years).

T h e results of later studies (108)

(5-8

i n d i c a t e d that m o l y b d e n u m

m i g h t b e i n v o l v e d , a n d the l o w e r caries experience of N a p i e r c h i l d r e n w a s the result of a h i g h e r M o a v a i l a b i l i t y f r o m the s o i l w h i c h c a u s e d increases i n the m i n e r a l c o m p o s i t i o n of vegetables c o n s u m e d i n the area. A n d e r s o n (5,6)

Recently,

r e p o r t e d first a s t u d y w i t h 270 c h i l d r e n a n d t h e n another

s t u d y w i t h l a r g e r n u m b e r s of c h i l d r e n f r o m the Somerset area i n E n g l a n d . Downloaded by UNIV OF PITTSBURGH on May 4, 2015 | http://pubs.acs.org Publication Date: June 1, 1970 | doi: 10.1021/ba-1970-0094.ch009

T h i s r e g i o n is one i n w h i c h cattle suffer f r o m m o l y b d e n u m p o i s o n i n g . W h e n the D M F f r o m the c h i l d r e n i n the c o n t r o l areas w a s c o m p a r e d w i t h the D M F f r o m c h i l d r e n i n t h e h i g h M o areas, i t w a s f o u n d t h a t t h e latter h a d better t h a n a 2 0 % r e d u c t i o n i n D M F . O t h e r e p i d e m i o l o g i c a l studies h a v e suggested that h i g h levels of c e r t a i n elements s u c h as s e l e n i u m i n the s o i l m a y b e associated w i t h h i g h caries i n c i d e n c e

(68).

I n this c o u n t r y , N i z e l a n d B i b b y (141) b e t w e e n soils a n d caries p r e v a l e n c e .

d e m o n s t r a t e d correlations

T h e highest p r e v a l e n c e of caries

i n the U n i t e d States is f o u n d i n the N e w E n g l a n d states associated w i t h p o d z o l s . T h e s e soils are g e n e r a l l y s t r o n g l y a c i d a n d of n a t u r a l f e r t i l i t y . T h e l o w e s t i n c i d e n c e of caries is f o u n d i n the s o u t h w e s t e r n states w h e r e the s e m i - a c i d soils are p o t e n t i a l l y h i g h i n m i n e r a l nutrients f o r t h e y h a v e n o t b e e n exposed to the l e a c h i n g a n d erosion a c t i o n f o r l o n g p e r i o d s of time.

F l u o r i d e i n these soils d e f i n i t e l y c o n t r i b u t e s to this l o w caries

p r e v a l e n c e , b u t i n the D a k o t a s w h e r e w a t e r h i g h i n fluoride is c o m m o n , there is a f a i r l y h i g h p r e v a l e n c e of caries. T h i s i n d i c a t e s that factors other t h a n fluoride are i n f l u e n c i n g the caries p i c t u r e . Dietary Minerals, F o o d Ashes, and

Experimental Dental Caries.

M i n e r a l s i n diets h a v e a p r o f o u n d effect o n the d e n t a l caries experience of e x p e r i m e n t a l a n i m a l s . Sognnaes a n d S h a w (172,

173)

o b s e r v e d m o r e caries lesions w h e n

rats w e r e g i v e n a p u r i f i e d r a t i o n that w a s c o m p l e t e i n k n o w n essentials t h a n w h e n this r a t i o n w a s s u p p l e m e n t e d w i t h 2 % of its o w n ash.

They

suggested

trace

that

p r o t e c t i o n against

elements i n the ash.

I n the

fight

caries

resulted f r o m certain

of w h a t is k n o w n t o d a y a b o u t

the

cariostatic effect of p h o s p h a t e , this also c o u l d b e e x p l a i n e d as a r i s i n g f r o m the P content of the ash. K e y e s (96)

o b s e r v e d a n increase i n caries

a c t i v i t y w h e n hamsters w e r e f e d a m i n e r a l - d e f i c i e n t diet. A s i m i l a r effect w a s r e p o r t e d b y G u s t a f s o n (64)

w h o n o t e d a m a r k e d increase i n caries

d e v e l o p m e n t w h e n the a m o u n t of salt m i x t u r e i n the d i e t w a s decreased. T h e ashes of different foods decrease the i n c i d e n c e of caries: c o r n ( 7 5 ) , b o n e (8, 84),

a n d c o c o a (97, 1 5 5 ) .

C o c o a ash has b e e n r e p o r t e d

i n a c t i v e as a cariostatic agent b y W y n n et al. (214),

b u t Stralfors


(183,

9.

Effect of

N A V I A

184, 185)

127

Minerals

f o u n d activity i n the w h o l e defatted

p o u n d s (186)

cocoa.

Phenolic

com-

present i n c o c o a m i g h t b e i n v o l v e d i n this effect. O f these

foods, c o r n is t h e most i m p o r t a n t since i t is c o m m o n l y eaten b y m a n k i n d . I n 1950 (142),

N i z e l a n d H a r r i s r e p o r t e d t h a t diets c o n t a i n i n g c o r n a n d

m i l k g r o w n i n T e x a s c a u s e d o n l y 4 0 % as m u c h d e n t a l d e c a y i n hamsters as c o r n a n d m i l k g r o w n i n N e w E n g l a n d . T h i s effect w a s n o t c a u s e d b y fluorine fluoride (144)

since t h e F content w a s m a d e e q u a l b y t h e a d d i t i o n of s o d i u m to t h e N e w E n g l a n d diet.

L a t e r , these investigators

reported

t h a t these differences i n d i c a t e t h e presence of a c a r i o g e n i c

factor


i n t h e N e w E n g l a n d c o r n a n d m i l k rather t h a n t h e presence o f a c a r i o static f a c t o r i n t h e T e x a s c o r n a n d m i l k .

Reasoning that t h e cariogenic

f a c t o r i n N e w E n g l a n d foods w a s a trace element, N i z e l a n d H a r r i s

(143)

t r i e d t o m a g n i f y t h e effect b y s u p p l e m e n t i n g t h e N e w E n g l a n d d i e t w i t h its a s h ( 5 5 0 ° C ) . C o n t r a r y t o expectations, t h e caries score of t h e hamsters f e d t h e a s h - s u p p l e m e n t e d d i e t w a s o n l y 3 5 % as h i g h as t h e c o n t r o l g r o u p . T h i s o b s e r v a t i o n l e d to a n i n v e s t i g a t i o n to i d e n t i f y t h e cariostatic factor i n t h e f o o d a s h . T h e c o m p o s i t i o n of this a s h w a s d e t e r m i n e d b y c h e m i c a l a n d s p e c t r o g r a p h i c m e t h o d s , a n d a salt w a s p r e p a r e d c a t i n g t h e 11 m i n e r a l elements that c o u l d b e q u a n t i t a t e d . hamsters,

dupli-

W h e n f e d to

this salt m i x t u r e w a s s i g n i f i c a n t l y m o r e cariostatic

than the

ash w h i c h i t i m i t a t e d ( 7 5 ) . T h i s result c o u l d i n d i c a t e t h a t o n e ( o r m o r e ) of t h e t r a c e elements i n t h e f o o d a s h w h i c h c o u l d n o t b e q u a n t i t a t e d a n d w a s , therefore, o m i t t e d f r o m t h e salt m i x t u r e , is a strong c a r i o g e n i c agent. I n o r d e r to investigate this p h e n o m e n o n f u r t h e r , H a r r i s a n d N i z e l (74)

f e d hamsters five diets c o n t a i n i n g different c o m b i n a t i o n s of the 11

elements s u p p l e m e n t e d to a c a r i e s - p r o m o t i n g diet. W h e n t h e p h o s p h o r u s c o m p o n e n t ( K H 0 P O 4 ) w a s o m i t t e d , t h e caries score rose f r o m 0.7 to 18.4. S i n c e t h e score of the c o n t r o l g r o u p w a s 13.4, i t w a s e v i d e n t that some of t h e 10 m i n e r a l elements i n t h e P-free salt m i x t u r e m i g h t b e a c t u a l l y c a r i o g e n i c . C o n s t a n t et al. (42) c a r r i e d o u t studies c o m p a r i n g w h o l e cereals w i t h processed a n d p u r i f i e d cereals. T h e y f o u n d that w h o l e cereals w e r e less c a r i o g e n i c t h a n t h e p u r i f i e d processed p r o d u c t .

T h e y also

investigated

the c a r i o g e n i c i t y o f a l k a l i n e a s h foods a n d t h a t of a c i d a s h foods a n d f o u n d n o significant difference u n d e r the e x p e r i m e n t a l c o n d i t i o n s u s e d . L a t e r , t h e y s t u d i e d (43,

44)

t h e effect o n caries o f a c i d i c a n d b a s i c

minerals a n d f o u n d that acidic inorganic, basic, or acidic organic

salt

m i x t u r e s gave n o p r o t e c t i o n against t o o t h d e c a y , w h i l e a h i g h l e v e l of b a s i c i n o r g a n i c salts r e s u l t e d i n a m a r k e d decrease i n t o o t h d e c a y . M i l l e r (118)

r e p o r t e d that d o u b l i n g t h e H u b b e l l - M e n d e l - W a k e m a n

salt m i x t u r e f r o m 1.2 grams

to 2.4 g r a m s / 1 0 0 grams

gave

a marked

r e d u c t i o n i n the n u m b e r of carious teeth, t h e n u m b e r of carious areas, a n d t h e caries score. T h i s effect w a s v e r i f i e d a g a i n i n a s e c o n d e x p e r i m e n t


128

DIETARY

C H E M I C A L S

VS.

D E N T A L

CARIES

b u t the effect w a s n u l l i f i e d w h e n 1 2 % of p o w d e r e d sucrose w a s u s e d i n p l a c e of a n e q u a l a m o u n t of r i c e

flour.

E v e n t h o u g h there is a definite r e l a t i o n b e t w e e n d i e t a r y t r a c e elements a n d d e n t a l caries, there is n o c e r t a i n k n o w l e d g e of the m e c h a n i s m t h r o u g h w h i c h these elements influence caries. Some of the p o s s i b l e w a y s i n w h i c h t h e y c o u l d act are t h e f o l l o w i n g : ( 1 ) I n c o r p o r a t i n g trace elements p r e - e m p t i v e l y i n t o the t o o t h m i n e r a l to c h a n g e its p h y s i c o - c h e m i c a l properties.


( 2 ) I n f l u e n c i n g the c e l l u l a r e n z y m e systems i n v o l v e d i n the e r a l i z a t i o n of the teeth. ( 3 ) A l t e r i n g p r e - e m p t i v e l y the m a t r i x of the tooth.

nature

of

the

min-

calcifying organic

( 4 ) E n h a n c i n g or i n h i b i t i n g the d e p o s i t i o n of m i n e r a l elements s u c h as fluoride or p h o s p h o m s o n the e n a m e l surface a n d t h e r e b y i n f l u e n c i n g the p o s t - e r u p t i v e m a t u r a t i o n of h y p o r n i n e r a l i z e d e n a m e l areas. ( 5 ) C h a n g i n g t h e p h y s i c a l a n d c h e m i c a l characteristics of s a l i v a . (6)

I n t e r f e r i n g d i r e c t l y w i t h the r e p r o d u c t i o n , m e t a b o l i s m , a n d i m p l a n t a t i o n of 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 o n the t o o t h surface.

M e t a l Ions as E n z y m e A c t i v a t o r s i n M i c r o b i a l C e l l s . M e t a l s m a y enter e n z y m e reactions as cofactors or activators w h i c h b r i n g the e n z y m e i n t o a c a t a l y t i c a l l y a c t i v e state. T h e a c t i v i t y of enzymes is affected b y the presence or absence of m i n e r a l salts, the n a t u r e of the ions present, a n d t h e i r concentrations. C e r t a i n ions are necessary f o r t h e a c t i v i t y of the e n z y m e , w h i l e others—i.e., A g , H g , P b — m a y b e h i g h l y toxic. +

2 +

2 +

It is

a characteristic of these systems that c e r t a i n ions are poisonous f o r some enzymes a n d activators f o r others.

Some m a y i n h i b i t a n e n z y m e at one

c o n c e n t r a t i o n a n d yet activate the same e n z y m e at another c o n c e n t r a t i o n . T h e effects of metals o n enzymes m a y b e p r o d u c e d b y m a n y m e t a b o l i c routes, a n d i n most cases h a v e not b e e n i d e n t i f i e d . T h e a c t i v a t i n g effect u s u a l l y is not specific. T h e e n z y m e f u m a r a s e m a y be a c t i v a t e d b y several m e t a l ions, yet other e n z y m e s s u c h as i n o r ganic pyrophosphatase specifically require M g

2 +

w h i c h cannot be replaced

b y others. A p p r o x i m a t e l y 16 different m e t a l cations activate one or m o r e enz y m e s ; these are: Al + Ca Cd + Co 3

2 +

2

2 +

Mg

2 +

Cr»+ Cs+ Cu Fe

2 +

2 +

K+ Mg + Mn + Mo+ 2

2

Na+ Ni Rb+ Zn + 2 +

2

is the n a t u r a l a c t i v a t o r of a great m a j o r i t y of the e n z y m e s w h i c h

act o n p h o s p h o r y l a t e d substrates, s u c h as the p h o s p h o k i n a s e s , the s y n -


9.

Effect of

N A V I A

129

Minerals

thetases, a n d the enzymes w h i c h h y d r o l y z e p h o s p h o r i c a c i d a n h y d r i d e s , b u t not the phosphorylases. I n most cases, M g b u t not b y other metals. and

2 +

can be replaced b y M n

S o d i u m can be replaced b y K

M n , Co , N i , and Z n 2 +

2 +

2 +

+

i n some cases,

m a n y times are i n t e r c h a n g e a b l e

2 +

2 +

among

t h e m . A n t a g o n i s m is f a i r l y c o m m o n , a n d N a m a y act as a c o m p e t i t i v e +

inhibitor for K with M g

2 +

2 +

i n h i b i t s the C a

2 +

Ca

2 +

competes

adenosinetriphosphatase,

a c t i v a t i o n of m y o s i n a d e n o s i n e t r i p h o s p h a -

E n z y m e s also m a y b e affected

c e r t a i n anions. Downloaded by UNIV OF PITTSBURGH on May 4, 2015 | http://pubs.acs.org Publication Date: June 1, 1970 | doi: 10.1021/ba-1970-0094.ch009

a c t i v a t i o n (i.e., p h o s p h o t r a n s a c e t y l a s e ) ,

to i n h i b i t c e r t a i n e n z y m e s , s u c h as

a n d also M g tase.

+

c o n s i d e r a b l y b y the presence of

S a l i v a r y a l p h a amylases, for e x a m p l e , are affected

greatly b y c h l o r i d e s that this i o n has b e e n activator of these e n z y m e s M a c D o n a l d (116)

r e g a r d e d as the

so

natural

(129).

has discussed the m i c r o b i o l o g y of caries, stressing

that i t is a b a c t e r i a l l y - i n d u c e d disease c h a r a c t e r i z e d b y a d e c a l c i f y i n g a c t i o n o n the m i n e r a l c o m p o n e n t s a n d a p r o t e o l y t i c a c t i o n o n the o r g a n i c components.

G i v e n energy a n d n i t r o g e n sources, the o r a l m i c r o b i o t a , i n

c o m m o n w i t h a l l m i c r o o r g a n i s m s , w i l l not g r o w i n the c o m p l e t e absence of c e r t a i n m i n e r a l elements.

A s discussed a b o v e , this is b e c a u s e of the

role of metals as i o n activators of the e n z y m e systems essential f o r m e t a b o l i c a c t i v i t y . It w o u l d b e of interest to d e t e r m i n e the specific n u t r i t i o n a l needs f o r trace elements of the c a r i o g e n i c s t r e p t o c o c c i a n d c o m p a r e t h e m w i t h those of the n o n c a r i o g e n i c streptococci.

B o w e n (17)

a t t e m p t e d to

o b t a i n s u c h i n f o r m a t i o n a n d r e p o r t e d that of the three cations tested (manganese, c a l c i u m , a n d m a g n e s i u m ) o n l y manganese is an essential r e q u i r e ment f o r g r o w t h .

A l t h o u g h no q u a l i t a t i v e differences

were

observed

c o n c e r n i n g the r e q u i r e m e n t s f o r g r o w t h of c a r i o g e n i c a n d n o n c a r i o g e n i c organisms, some discrepancies i n t h e i r q u a n t i t a t i v e needs w e r e r e p o r t e d w h i c h w a r r a n t f u r t h e r research. T h e m i n e r a l s f o u n d i n the surface e n a m e l a n d those s u p p l i e d b y the diet, the s a l i v a , a n d d e s q u a m e n t e d

tissue cells m a y influence the o r a l

m i c r o b i o t a i n the f o l l o w i n g w a y s : s t i m u l a t i o n of g r o w t h (increase i n c e l l n u m b e r s ) , f a c i l i t a t i o n of attachment of cells to e n a m e l surface, i n f l u e n c i n g the f o r m a t i o n of m e t a b o l i c e n d p r o d u c t s i n c l u d i n g i n t r a - a n d extracellular

polysaccharides,

inhibition

of

growth

or

metabolic

activity

t h r o u g h p o i s o n i n g of e n z y m e systems w i t h i n the cells, a n d m o d i f i c a t i o n of o r a l e n v i r o n m e n t b y s t i m u l a t i o n of g r o w t h of c e r t a i n types of cells, thus i n h i b i t i n g others. Mineral Composition of Teeth in Humans and Experimental

Animals

Inorganic Composition of Bones and Teeth. B o n e a n d t o o t h m i n e r a l is m a d e u p m o s t l y of c a l c i u m a n d p h o s p h a t e i n the f o r m of apatite, yet m a n y other elements

are f o u n d w i t h i n its structure.

Bone and tooth


130

DIETARY

C H E M I C A L S

VS.

D E N T A L

CARIES

m i n e r a l , therefore, is n o t a single homogeneous c h e m i c a l c o m p o u n d b u t a m i x t u r e w h i c h varies i n c o m p o s i t i o n a n d d i s t r i b u t i o n . O n e of t h e p r o b l e m s i n d e f i n i n g t h e c h e m i c a l b e h a v i o r of t h e i n o r g a n i c p o r t i o n of t h e teeth is t h e d i f f i c u l t y i n d i f f e r e n t i a t i n g b e t w e e n the constituents of t h e b a s i c structure, t h e ions h a v i n g o n l y a surface r e l a t i o n s h i p to t h e crystals, a n d those p o s s i b l y c o m b i n e d w i t h t h e apatite crystals i n a separate phase.

T h e r e f o r e , e v e n t h o u g h t h e structure a n d

c o m p o s i t i o n of t h e m i n e r a l corresponds closely to t h a t of h y d r o x y a p a t i t e , s u b s t a n t i a l amounts of c a r b o n a t e a n d citrate are f o u n d as w e l l as i o n Downloaded by UNIV OF PITTSBURGH on May 4, 2015 | http://pubs.acs.org Publication Date: June 1, 1970 | doi: 10.1021/ba-1970-0094.ch009

substitutions i n t h e c r y s t a l lattice. T h e m i n u t e crystals a n d interspaces b e t w e e n t h e m expose a large surface area to t h e e n v i r o n m e n t fluids a n d as a result d i s s o l u t i o n a n d r e c r y s t a l l i z a t i o n m a y take p l a c e , m a i n t a i n i n g a d y n a m i c b a l a n c e .

This

large surface area of b o n e a n d t o o t h m i n e r a l s influences its t o t a l c o m p o s i t i o n i n t w o w a y s , b y a d s o r b i n g o r s u b s t i t u t i n g ions as w e l l as i n c o r p o r a t i n g some of t h e m w i t h i n surface u n i t cells w i t h u n s h a r e d sides a n d b y i s o i o n i c o r h e t e r o i o n i c exchange w i t h the fluids b a t h i n g the crystals. I n g e n e r a l , t h e elements w h i c h l o c a l i z e i n b o n e a n d teeth are r e f e r r e d to as "bone-seekers"

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

substances s u c h as m u r e x i d e a n d t h e tetracyclines w h i c h c o m b i n e a v i d l y w i t h b o n e o r t o o t h at n e w c a l c i f i c a t i o n a n d also at carious sites. Table I. Composition of Outer and Inner Enamel of Teeth from H u m a n Subjects Living in Different Geographic Areas 0

\LMol.

Outer Carbonate Sodium Fluoride Magnesium Zinc Citrate Aluminum Strontium Lactate Lead Copper Silica Silver Iron Tin Manganese

Enamel

350-440 230-360 17-176 30-60 6.6-27.5 3.5-5.0 1.4-4.8 0.3-3.7 -2.9 0.4-2.6 0.1-1.8 0.2-1.5 tr-0.9 0.4-0.6 tr-0.4

0.1-0.4

per

Gram

Body

Enamel

525-654 310-380 3.8-44 60-74 2.9-14.2 -1.1 1.1-4.5 0.7-4.6 -1.2 0.1-1.1 tr-0.6 0.1-1.8 0.0-0.5 0.2-0.4 0.0-0.3 0.1-0.2

° Data from Ref. 24.


9.

Effect of

N A V I A

Table II.

Major Inorganic Constituents of H u m a n Enamel" Thermal Activation

Constituent

1.16 db 0.40 0.36 db 0.04 0.65 zb 0.30


K

-

Data from Ref. 175 and 176. Table III.

Minor Inorganic Constituents of H u m a n Enamel" Thermal Neutron Activation Analysis

Constituent

F

Chemical Analysis

62-650 8-218 152-227 50-400

388 zb 109 276 + 106 94 ± 22 4.9 zb 1.6 4.6 ± 1.1 0.24 zb 0.12 0.26 zb 0.11 0.54 zb 0.08 0.02 zb 0.01 0.0049 zb 0.0012 0.0027 zb 0.0016 0.00024 db 0.00009 > 10>10~

Fe

Zn Sr Rb Br

W Cu

Mn Au

Ag Cr Co v

10-100 0-18 0-100

5

Pt 0

33.6-39.4 16.1-18.0 1.92-2.17 1.95-3.66 0.25-0.90 0.25-0.56 0.19-0.30 0.05-0.30

-

2

Na Mg CI 0

Chemical Analysis

Neutron Analysis

37.4 zb 1.0 18.3 =fc 2.2 2.04

Ca P Ca/P

C0

131

Minerab

6

Parts per million, dry weight; data from Ref. 175 and 176. T h e chemical composition of enamel, dentin, cementum, a n d p u l p

has b e e n d i s c u s s e d b y Z i p k i n ( 2 1 7 ) , w h o also d i s c u s s e d the c h e m i s t r y o f the s o u n d a n d carious e n a m e l . Brudevold

(24, 30)

reported

o n t h e trace

m i n e r a l content

of

teeth c o l l e c t e d f r o m h u m a n beings l i v i n g i n different g e o g r a p h i c areas. T h e concentrations o f these elements ( / j t M / g r a m ) o f t h e surface e n a m e l a n d the b o d y o f the i n t a c t e n a m e l are p r e s e n t e d i n T a b l e I. T h e a m o u n t s i n t h e outer e n a m e l w e r e often, b u t not a l w a y s , h i g h e r t h a n a m o u n t s i n the i n n e r e n a m e l , a n d the r a n g e o f values is q u i t e w i d e . S o r e m a r k a n d c o w o r k e r s (175, 176), u s i n g n e u t r o n a c t i v a t i o n analysis, r e p o r t e d values f o r t o t a l h u m a n e n a m e l ( T a b l e s II, III).


132

DIETARY

S t e a d m a n et al. (179)

C H E M I C A L S

VS.

D E N T A L

CARIES

a n a l y z e d the ancient teeth of P u e b l o I n d i a n s

(800 years o l d ) a n d I n d i a n K n o l l (5000 years o l d ) f o r the same elements a n d f o u n d that t h e y o c c u r r e d i n greater c o n c e n t r a t i o n i n t h e outer t h a n i n the i n n e r layers of e n a m e l . F l u o r i d e w a s f o u n d i n greatest c o n c e n t r a t i o n i n the external e n a m e l , f o l l o w e d b y Z n , S i , M n , P b , A g , C u , a n d S n . T h e y n o t e d a r e m a r k a b l e s i m i l a r i t y i n the d i s t r i b u t i o n of m a n y trace elements b e t w e e n a n c i e n t a n d c o n t e m p o r a r y A m e r i c a n teeth.

Contrary

to expectations, t h e y f o u n d b u t l i t t l e p e n e t r a t i o n of trace elements i n t o the b u l k of the t o o t h structure, e v e n i n teeth of 5000 years o l d . A s g a r ( 7 ) Downloaded by UNIV OF PITTSBURGH on May 4, 2015 | http://pubs.acs.org Publication Date: June 1, 1970 | doi: 10.1021/ba-1970-0094.ch009

s t u d i e d differences i n the d e n t i n a n d e n a m e l of ancient G r e e k a n d A m e r i c a n teeth, b u t his samples w e r e too f e w to p e r m i t conclusions. Hadjimarkos a n d Bonhorst (69)

s t u d i e d 27 s o u n d a n d 17 carious

teeth f r o m 2 0 - 4 0 y e a r o l d m o d e r n A t h e n i a n s , a n d 14 s o u n d teeth f r o m the skulls of five w o m e n a n d f o u r m e n w h o l i v e d i n 800 a n d 1100 B . C . ( T a b l e I V ) . H e a t t r i b u t e d the h i g h i m m u n i t y to caries of A t h e n s s c h o o l c h i l d r e n to the h i g h i n t a k e of fluoride a n d p o s s i b l y the l o w e r i n t a k e of selenium. Table I V .

Mineral Content of Greek Teeth Modern

Fluorine, p p m Selenium, p p m

Greek

Ancient

Enamel

Dentine

Enamel

178 0.03

0.13

374 0.13

Greek Dentine 0.45

S e v e r a l attempts h a v e b e e n m a d e to correlate v a r i a t i o n s i n t h e m i n e r a l content of d e n t a l tissues w i t h caries sensitivity. P i c a r d et al.

(148)

d i v i d e d 120 h u m a n teeth i n t o three g r o u p s : h e a l t h y , s u p e r f i c i a l caries, a n d d e e p caries.

T h e y f o u n d n o significant difference i n the ash, C a , a n d P

content, or i n the C a / P r a t i o of the e n a m e l of the three g r o u p s . T h e ash, C a , a n d P content of the d e n t i n f r o m d e e p carious lesions w e r e signific a n t l y l o w e r t h a n i n the h e a l t h y teeth. T h e same t r e n d w a s n o t e d i n the teeth w i t h s u p e r f i c i a l caries, b u t the t r e n d was n o t significant. (105)

Lobene

s t u d i e d the i n o r g a n i c constituents of the e n a m e l a n d d e n t i n of teeth

f r o m hamsters, a n d c o n c l u d e d that the C a , P , a n d M g content of the d e n t i n d i d n o t v a r y greatly, w h a t e v e r the source. Z i p k i n a n d P i e z (218)

t r i e d to correlate the c i t r i c a c i d content of

h u m a n teeth w i t h s u s c e p t i b i l i t y to caries i n a s t u d y o f 65 samples of s o u n d d e n t i n a n d 129 samples of carious d e n t i n . T h e y f o u n d 888 ± a n d 872 ±

103 m g %

105 m g % c i t r i c a c i d i n the s o u n d a n d carious d e n t i n , respec-

t i v e l y , a n d thus n o e v i d e n c e of a c o r r e l a t i o n b e t w e e n c i t r i c a c i d a n d d e n t a l caries. Studies of this t y p e are difficult to i n t e r p r e t , f o r the a n a l y sis is m a d e o n the carious m a t e r i a l left after the disease has p r o g r e s s e d a n d n o i n f o r m a t i o n is a v a i l a b l e as to the c o n c e n t r a t i o n of m i n e r a l s before t h e carious l e s i o n started.


9.

Effect of

N A V I A

Minerals

133

Trace Element Distribution in Teeth. T h e d i s t r i b u t i o n of i n d i v i d u a l elements i n h u m a n teeth has b e e n s t u d i e d b y B r u d e v o l d (24) associates.

T h e r a n g e of c o p p e r (47)

a n d his

i n f o u r successive g r i n d i n g s of the

e n a m e l of h u m a n teeth w a s 15 to 30 p p m , a n d its d i s t r i b u t i o n w a s r a n d o m a n d u n a f f e c t e d b y age.

T h e t i n content of p o o l e d samples (28)

of f o u r

successive layers of e n a m e l was 7.0 p p m i n the outer t w o layers a n d n i l i n the t h i r d a n d f o u r t h layers. L e a d (27)

w a s highest (550 p p m ) i n the outer

e n a m e l layers of e r u p t e d teeth a n d decreased to a rather constant l e v e l (90 p p m ) i n t h e i n n e r m o s t layers. Z i n c (31) Downloaded by UNIV OF PITTSBURGH on May 4, 2015 | http://pubs.acs.org Publication Date: June 1, 1970 | doi: 10.1021/ba-1970-0094.ch009

and

fluoride.

was distributed like lead

It w a s h i g h e r o n the surface ( 4 3 0 - 2 1 0 0 p p m ) , l o w e r i n the

subsurface layers, a n d w a s d e p o s i t e d i r r e g u l a r l y o n the surface. L i t t l e a n d B r u d e v o l d (104)

f o u n d differences i n the C 0

2

content of

t h e s u p e r f i c i a l a n d i n n e r layers of i n t a c t h u m a n e n a m e l i n e r u p t e d a n d u n e r u p t e d teeth.

I n a l l age g r o u p s , the c o n c e n t r a t i o n of c a r b o n d i o x i d e

i n c r e a s e d f r o m the surface t o w a r d the d e n t i n , b u t as the c a l c i f i c a t i o n proceeds d u r i n g d e v e l o p m e n t , t h e c a r b o n d i o x i d e content decreases. B o n e - s e e k i n g r a d i o a c t i v e isotopes H o l g a t e et al. (87) of r a b b i t s .

(i.e.,

Sr)

s t u d i e d the a c c u m u l a t i o n of S r

accumulate 90

i n teeth.

i n the d e n t a l tissues

A n increase i n c o n c e n t r a t i o n w a s o b s e r v e d d u r i n g 30 d a y s

f o l l o w i n g i n t r a v e n o u s i n j e c t i o n , a n d t h e n it f e l l a b r u p t l y . S i n c e t h e teeth of the r a b b i t g r o w c o n t i n u o u s l y , t h e S r

90

d e p o s i t e d i n the teeth m a y h a v e

b e e n lost w h e n the r a d i o a c t i v e z o n e w a s w o r n a w a y .

B u t l e r (33)

s e r v e d a n inverse c o r r e l a t i o n b e t w e e n the c o n c e n t r a t i o n of S r

90

ob-

a n d the

age o f h u m a n b e i n g s . T h e m i n e r a l c o m p o s i t i o n of teeth has b e e n s t u d i e d i n r e l a t i o n to d i s c o l o r a t i o n of the t o o t h substance.

Isaac a n d B r u d e v o l d (89)

studied

the p o s s i b l e s t a i n i n g properties of P b , S n , A g , H g , C u , a n d F e w h e n d e p o s i t e d i n the e n a m e l , a n d t h e n exposed t h e m to a s u l f u r - c o n t a i n i n g medium.

T h e s e m e t a l sulfides are b r o w n or b l a c k , a n d t h e y m a y b e

p r o d u c e d f r o m f o o d or s a l i v a u n d e r o r d i n a r y c o n d i t i o n s . T h e

surfaces

of the c r o w n s a n d roots of i n t a c t teeth w e r e treated w i t h solutions c o n t a i n i n g t h e cations, a n d a l l d e v e l o p e d d i s c o l o r a t i o n w h e n exposed to t h e s u l f u r - c o n t a i n i n g m e d i u m . O n the other h a n d , L a n d i n g et

al.

(101)

n o t e d that the teeth of a p a t i e n t w i t h hemosiderosis w e r e n o t p i g m e n t e d , e v e n t h o u g h t h e y c o n t a i n e d 50.8 / x g % of i r o n rather t h a n t h e 16.1 / x g % i n c o n t r o l patients. It is not k n o w n w h e t h e r the F e w a s d e p o s i t e d i n the teeth b e f o r e or after e r u p t i o n . P o s s i b l y , the l o c a t i o n of t h e F e i n t h e t o o t h determines whether it w i l l be reactive. D u r i n g the last 10 years, investigators h a v e b e e n m a k i n g use of a n a l y t i c a l p r o c e d u r e s b a s e d o n p h y s i c a l p r i n c i p l e s to q u a n t i t a t e elements i n teeth a n d bones.

U s i n g n e u t r o n a c t i v a t i o n analysis, S o r e m a r k a n d

c o w o r k e r s ( 1 0 9 , 1 7 4 , 175,176)

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

h u m a n erupted and unerupted enamel.

N i x o n et

al.

(138,

139,


140)

134

DIETARY

s t u d i e d t h e c o p p e r , arsenic,

C H E M I C A L S

VS.

D E N T A L

CARIES

a n d a n t i m o n y levels i n h u m a n

enamel.

M a n g a n e s e also has b e e n e s t i m a t e d i n h u m a n e n a m e l b y these same investigators (137)

a n d b y B a t t i s t o n e et

al(ll).

T h e i n o r g a n i c c o m p o n e n t s of teeth also h a v e b e e n a n a l y z e d b y s u c h m e t h o d s as x-ray e m i s s i o n s p e c t r o g r a p h y s p e c t r o g r a p h y (188).

(38)

a n d spark source

mass

T h i s last m e t h o d continues t o p l a y a n extremely

i m p o r t a n t role i n e l e m e n t a l a n d trace analysis because of great sensitivity f o r metals a n d nonmetals. I n general, these m e t h o d s h a v e b e e n u s e f u l i n d e t e c t i n g a n d q u a n t i Downloaded by UNIV OF PITTSBURGH on May 4, 2015 | http://pubs.acs.org Publication Date: June 1, 1970 | doi: 10.1021/ba-1970-0094.ch009

t a t i n g trace quantities of elements i n teeth a n d b o n e , b u t t h e d e v e l o p m e n t of t h e electron p r o b e m a d e possible t h e d e t e r m i n a t i o n of t h e d i s t r i b u t i o n of elements i n m i c r o s t r u c t u r e s .

E q u i p m e n t to p r o d u c e beams of ions,

protons, electrons, a n d x-rays is n o w a v a i l a b l e to b e u s e d i n e x p l o r i n g the c r y s t a l l i n e n a t u r e of solids a n d b i o l o g i c a l tissues. T h e e l e c t r o n p r o b e has b e e n u s e d i n m e t a l l u r g y a n d m i n e r o l o g y , b u t its a p p l i c a b i l i t y to b i o l o g i c a l samples has b e e n l i m i t e d b y t h e fact that l i g h t elements w h i c h are of great interest to t h e b i o l o g i s t h a v e n o t b e e n d e t e c t e d easily a n d the p h y s i c a l properties of b i o l o g i c a l specimens are different f r o m those samples n o r m a l l y s t u d i e d i n m e t a l l u r g y . T o d a y , n e w i m p r o v e m e n t s i n e q u i p m e n t a n d m e t h o d o l o g y are m a k i n g p o s s i b l e t h e a p p l i c a t i o n of this v a l u a b l e a n a l y t i c a l t o o l to samples of b i o l o g i c a l o r i g i n (4, 197, 198). T h e m i n e r a l i z e d tissues of the b o d y , s u c h as bones a n d teeth, l e n d themselves to s t u d y b y t h e p r o b e . A n a r r o w b e a m of electrons is f o c u s e d o n a s m a l l area of the s a m p l e (less t h a n 1 m i c r o n i n d i a m e t e r ) , a n d t h e x-rays r e s u l t i n g f r o m t h e electron b o m b a r d m e n t are c o l l e c t e d at a p r e d e t e r m i n e d angle a n d a n a l y z e d i n o n e o r m o r e spectrometers.

These

analyses c a n b e m a d e q u a n t i t a t i v e b y c o m p a r i n g the counts p e r m i n u t e o b t a i n e d w i t h those f r o m suitable standards.

B i r k s (16)

described the

i n s t r u m e n t a n d its use i n a v a r i e t y of a n a l y t i c a l a p p l i c a t i o n s . C a m p b e l l a n d B r o w n ( 3 9 ) r e v i e w e d t h e significant progress m a d e i n t h e last f e w years. U s i n g t h e electron p r o b e , Rosser et al. (154)

studied the C a concen-

tration i n developing enamel, a n d Boyde, Switsur, a n d Fearnhead

(19)

s t u d i e d t h e c a l c i u m a n d i r o n d i s t r i b u t i o n i n rat e n a m e l a n d h u m a n m o l a r enamel.

T h e s e investigators r e p o r t e d a h i g h e r c o n c e n t r a t i o n of c a l c i u m

i n t h e p e r i t u b u l a r area of d e n t i n t h a n i n t h e i n t e r t u b u l a r area. et al. (189),

u s i n g a n electron m i c r o s c o p e w i t h a n x-ray

Takuma

spectrometer

attachment, e x a m i n e d horse d e n t i n p r e p a r e d f o r r o u t i n e electron m i c r o s c o p y (500 A t h i c k ) . T h e y f o u n d t w i c e as m u c h C a a n d P i n t h e p e r i t u b u l a r as i n t h e i n t e r t u b u l a r m a t r i x , a l t h o u g h t h e y c o u l d n o t d e t e r m i n e a statistical difference i n t h e P K a • C a K Z n , a n d T l a l l cause decreased c a l c i f i c a t i o n .

When

Sr

a n d V w e r e absent, caries i n c r e a s e d ; w h e n present, caries w a s c o n t r o l l e d . D e l e t i o n o f Z n , B a , a n d T l f r o m the d i e t h a d n o effect o n d e n t a l caries. T h i s result p r o m p t e d G e y e r (60)

to test V i n s m a l l groups of h a m -

sters. M a r k e d l y less e n a m e l caries w a s o b s e r v e d i n hamsters f e d d a i l y 0.08 mg V O 2

s

i n c o m p a r i s o n w i t h controls o n the c a r i o g e n i c d i e t , a n d d e n t i n a l

caries also w a s s t o p p e d . H e suggested t h a t . . v a n a d i u m ions, i m b e d d e d i n e n a m e l a n d d e n t i n , c o u l d increase the hardness of the h y d r o x y l apatite as w e l l as the c o h e s i o n b e t w e e n the o r g a n i c a n d i n o r g a n i c m a t t e r . " H e i n a n d W i t s o t z k y (81)

f o u n d n o i n h i b i t i o n of caries i n hamsters

t h a t h a d b e e n g i v e n 10 p p m V i n the d r i n k i n g w a t e r .

A n increase i n

caries was n o t e d w h e n s l i g h t l y h i g h e r amounts w e r e g i v e n . toxic l e v e l of i n t a k e .

M u h l e r (121)

T h i s is a

f e d 10, 20, a n d 40 fig of v a n a d i u m

p e n t o x i d e p e r cc i n the d r i n k i n g w a t e r of rats a n d n o t e d n o effect o n caries w h e n these h i g h toxic levels of V w e r e g i v e n .


9.

NAVIA

Effect of

Minerals

145

T h e c o n c e n t r a t i o n of V g i v e n seems to b e i m p o r t a n t . W i n i k e r

(208)

f e d a salt of a m m o n i u m m e t a v a n a d a t e to hamsters a n d n o t e d caries i n h i b i t i o n w h e n 0.035 m g / d a y w e r e f e d a n d caries s t i m u l a t i o n w h e n 0.20 m g / d a y were given. M u n c h (128) given.

o b s e r v e d f a v o r a b l e results w h e n b o t h V a n d M o w e r e

H e p o s t u l a t e d that V acts l o c a l l y o n t h e teeth b y c h a n g i n g t h e

lattice of the h y d r o x y l apatite, w i t h V r e p l a c i n g P . Kruger

(100)

c o r i f i r m e d G e y e r i n a s t u d y o n rats b e g u n

during

amelogenesis i n the rat. R a t m o l a r caries w e r e r e d u c e d s i g n i f i c a n t l y . Downloaded by UNIV OF PITTSBURGH on May 4, 2015 | http://pubs.acs.org Publication Date: June 1, 1970 | doi: 10.1021/ba-1970-0094.ch009

H o w e v e r , S h a w a n d G r i f f i t h s (168)

o b s e r v e d n o effect w h e n v a n a d i u m

p e n t o x i d e o r v a n a d y l sulfate w a s f e d i n t h e d i e t o r i n t h e d r i n k i n g w a t e r . T h e r e w a s u n c e r t a i n t y i n t h e results w h e n t h e V salts w e r e f e d d u r i n g the d e v e l o p m e n t a l stage. T h e studies b y T a n k a n d S t o r v i c k ( 1 9 0 ) o n c h i l d r e n f r o m seleniferous a n d nonseleniferous areas i n d i c a t e a n i n v e r s e c o r r e l a t i o n b e t w e e n t h e V content of t h e w a t e r a n d caries d e v e l o p m e n t . S o m e studies h a v e b e e n m a d e of t h e i n t e r r e l a t i o n s h i p b e t w e e n

F

a n d V . T e m p e s t i n i (191) n o t e d that F a n d V together w e r e m o r e effective i n r e d u c i n g d e n t a l caries t h a n F alone. this

B u t t n e r (36)

d i d not confirm

finding. V deserves f u r t h e r i n v e s t i g a t i o n to d e t e r m i n e its effects o n b o n e a n d

t o o t h c a l c i f i c a t i o n a n d o n d e n t a l caries d e v e l o p m e n t . S T R O N T I U M .

T h i s b o n e - s e e k i n g a l k a l i n e e a r t h m e t a l appears to affect

caries. S h a w a n d G r i f f i t h s (168)

n o t e d n o e v i d e n c e of v a n a d i u m r e d u c i n g

d e n t a l caries i n c i d e n c e . R y g h ( 1 5 8 , 1 5 9 ) n o t e d a h i g h i n c i d e n c e of caries w h e n S r w a s absent f r o m the d i e t of rats. W h e n Sr a n d V w e r e a d d e d i n p l e n t y , caries w a s c u r t a i l e d . Johansen a n d H e i n 50 p p m of s t r o n t i u m as S r C l

2

(94)

c o n c l u d e d that

a d d e d to d r i n k i n g w a t e r h a d n o effect o n

hamsters' caries. B a n k s et al

(10)

r e p o r t e d that 1.0 to 2 . 0 % S r C l

2

a d d e d t o the d r i n k -

i n g w a t e r of w e a n l i n g rats c a u s e d c o n s i d e r a b l e d i s t u r b a n c e s

of t h e

c a l c i f i c a t i o n of t h e d e n t i n a n d c e m e n t u m . P i n d b o r g ( 1 5 1 ) m a d e a s i m i l a r o b s e r v a t i o n , a n d n o t e d a l a c k of p i g m e n t a t i o n of t h e n o r m a l e n a m e l of the rat i n c i s o r . S t e a d m a n et al

(178)

suggested that S r is d e p o s i t e d p r i -

m a r i l y before t h e e r u p t i o n a n d d u r i n g t h e c a l c i f i c a t i o n of t h e t o o t h , t h o u g h a d d i t i o n a l Sr is d e p o s i t e d i n the s e c o n d a r y d e n t i n a n d c e m e n t u m after

tooth

eruption.

a m o u n t s of S r

90

Therefore,

children will

deposit

considerable

w h e n there is h e a v y isotope f a l l o u t . B r y a n t et al

(32)

c o r r o b o r a t e d this c o n c l u s i o n , f o r t h e y f o u n d a n inverse c o r r e l a t i o n w i t h age.

B u t l e r (33)

f o u n d 2.6 ±

0.6 disintegrations o f S r ^ / m i n / g r a m i n

teeth o b t a i n e d f r o m c h i l d r e n u n d e r 4 years a n d 0.4 ±

0.2 i n teeth f r o m

h u m a n subjects o v e r 31 years of age.


146

DIETARY

Yaeger (215)

C H E M I C A L S

D E N T A L

VS.

CARIES

o b s e r v e d b y the use of a n electron m i c r o s c o p e t h a t the

m a t r i x of t h e fine structure of the h y p o m i n e r a l i z e d c o m p o n e n t p r o d u c e d by

Sr contained

pools of h e a v i l y stained

material, presumably nonfibrillar collagen.

homogeneous,

interfibrillar

This defect probably could

a c c o u n t f o r the i n h i b i t i o n of m i n e r a l i z a t i o n w h i c h results i n t h e h y p o m i n e r a l i z e d c o m p o n e n t of t h e incisors s t u d i e d . F u r t h e r studies of t h e role of Sr i n c a l c i f i c a t i o n a n d i n d e n t a l caries are n e e d e d . C o p p e r , a n essential element, is a constituent or a n activator

C O P P E R .


of c e r t a i n

enzymes,

a n d i t has a p o s t u l a t e d

role i n b o n e

formation

a n d i n m a i n t e n a n c e of m y e l i n w i t h i n t h e nervous system. C r i p p l i n g b o n e defects o c c u r i n cattle a n d sheep g r a z i n g o n C u - d e f i c i e n t pastures. Brudevold a n d Steadman

(26)

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

h u m a n teeth, a n d f o u n d n o c o r r e l a t i o n b e t w e e n C u content a n d t o o t h pigmentation

or caries.

M c C l u r e (113)

found no pronounced

effect w h e n C u w a s g i v e n i n d r i n k i n g w a t e r . S h a w (167)

caries

n o t e d n o effect

w h e n 0 . 5 % N a - C u c h l o r o p h y l l i n w a s a d d e d to t h e d r i n k i n g w a t e r of rats.

H o w e v e r , H e i n a n d S h a f e r ( 8 0 ) , u s i n g a p r e p a r a t i o n of N a - C u

c h l o r o p h y l l i n of 9 3 . 2 % p u r i t y , f o u n d a cariostatic effect i n hamsters. C o n c e n t r a t i o n s of 0.25 m g / 1 0 0 grams C u i n sucrose-containing s a l i v a d e f i n i t e l y i n h i b i t e d a c i d f o r m a t i o n w h i l e 3 to 4 m g / 1 0 0 grams C u i n s a l i v a c o m p l e t e l y i n h i b i t e d a c i d p r o d u c t i o n (56).

D r e i z e n et al. (52)

found no

r e l a t i o n b e t w e e n the C u content of s a l i v a a n d d e n t a l caries a c t i v i t y i n h u m a n subjects. T h e l e v e l o f C u n o r m a l l y present i n s a l i v a w a s u n a b l e in vitro to p r e v e n t the g r o w t h of L. Hein

(78)

acidophilus.

o b s e r v e d that C u S 0

r e d u c e d caries as t h e l e v e l w a s

4

i n c r e a s e d : 0, 10, 25, 50 p p m C u . A straight l i n e w a s o b t a i n e d w h e n t h e caries scores w e r e p l o t t e d against t h e l o g a r i t h m of t h e C u c o n c e n t r a t i o n , i n d i c a t i n g that t o o t h d e s t r u c t i o n w a s a n inverse f u n c t i o n o f t h e C u S 0 concentration.

K r u g e r (100)

injected 0.005 to 0.02 m g of C u N 0

3

4

intra-

p e r i t o n e a l l y i n t o rats, a n d n o t e d a caries r e d u c t i o n w h i c h a p p r o a c h e d the 5 % significance l e v e l . B O R O N .

T h i s w a s t h e first element t o b e p r o v e d essential f o r p l a n t

l i f e . It is n o t clear y e t w h e t h e r i t is a n essential e l e m e n t f o r a n i m a l s . W e s s i n g e r (205)

gave 200 m g B / k g b o d y w e i g h t as b o r i c a c i d a n d

o b s e r v e d n o e n a m e l h y p o p l a s i a i n the incisors. H e c o n c l u d e d that B h a d no effect o n amelogenesis K r u g e r (100)

i n contrast t o S r w h i c h has a m a r k e d effect.

gave 0.005 t o 0.025 m g B as b o r i c a c i d i n t r a p e r i t o n e a l l y , a n d

c o n c l u d e d that B is effective i n r e d u c i n g caries d e v e l o p m e n t . (168)

S h a w et al.

n o t e d a modest r e d u c t i o n i n caries w h e n 0.5, 1.0, a n d 2 . 0 % N a

borate were f e d post-developmentally. L I T H I U M .

Wisotzky and Hein

f o u n d n o effect o n a n i m a l caries.

(210)

tested l i t h i u m

sulfate a n d

H o w e v e r , Shaw a n d Griffiths


(168)

9.

ΝΑ V I A

Effect of Minerals

added a 0.1%

147

s u p p l e m e n t of l i t h i u m c a r b o n a t e to a rats' d i e t a n d o b

served a definite p o s t - d e v e l o p m e n t a l influence to i n h i b i t d e n t a l caries. G o l d , i n the f o r m of a u r i c c h l o r i d e , w a s r e p o r t e d b y W i s o t z k y

GOLD.

a n d H e i n (210)

to b e a potent i n h i b i t o r of caries i n hamsters.

Elements W i t h D o u b t f u l Caries Effect.

This alkaline

B E R Y L L I U M .

e a r t h m e t a l has b e e n r e p o r t e d to p r o d u c e changes i n b o t h bones a n d teeth.

M a y n a r d et al.

(112)

f e d w e a n l i n g rats a d i e t c o n t a i n i n g

BeSC>4 or B e C O e a n d o b s e r v e d r a c h i t i c lesions w i t h i n 3 weeks. (204)

fed 3 and 6%

levels of B e C 0

3

5%

Wentz

a n d o b s e r v e d rickets i f the v i t a


m i n D i n t a k e w a s l o w , as w e l l as e n a m e l h y p o p l a s i a a n d a p l a s i a , r e t a r d a t i o n i n c a l c i f i c a t i o n a n d i n d e n t i n f o r m a t i o n , a n d d e l a y e d e r u p t i o n of the teeth.

S h e r m a n a n d S o b e l (169)

r e p o r t e d that extremely l o w c o n c e n t r a

tions (0.01 p p m ) of B e i o n c a n l i m i t c a l c i u m p h o s p h a t e c r y s t a l g r o w t h , and

this m i g h t e x p l a i n the in vivo results.

R y g h (161)

c o n c l u d e d that

w h i l e F is essential to the p r o p e r f o r m a t i o n of t o o t h e n a m e l , B e is of n o significance. L e i c e s t e r et al. 0.02%

BeCl

2

(103)

f o u n d that w h e n m a l e hamsters w e r e g i v e n

i n d i e t or i n d r i n k i n g w a t e r f r o m the date of c o n c e p t i o n

u n t i l 24 days p o s t p a r t u m , a h i g h l y significant r e d u c t i o n i n d e n t a l d e c a y w a s o b s e r v e d 100 days later. and

T h e s e authors n o t e d (192)

that w h e n F e

F w e r e f e d together to m a l e hamsters, there w a s a statistically sig

nificant r e d u c t i o n i n caries. COBALT.

C o b a l t is a constituent of v i t a m i n B i

f o r m a t i o n , b u t n o definite r e l a t i o n b e t w e e n B been observed.

D r e i z e n et al.

(52)

i 2

2

w h i c h affects b l o o d

d e f i c i e n c y a n d caries has

f o u n d no r e l a t i o n b e t w e e n the C o

l e v e l i n s a l i v a of h u m a n beings a n d t h e i r caries experience. and

F o r s a i t h (82)

Hendershot

f o u n d 3 to 4 times m o r e caries i n m a l e rats f e d a

s u p p l e m e n t of C o - E D T A salt t h a n i n controls. C o b a l t m a y interfere w i t h the m i n e r a l i z a t i o n process, f o r G o l d e n b e r g (63)

n o t e d that the a d d i t i o n of C o (also B e , M n , N i ) to a b a s a l s o l u t i o n

w h i c h contained N a C l , K C 1 , and N a H C 0

3

accelerated

the i n a c t i v a t i o n

of the c a l c i f y i n g m e c h a n i s m of a n e p i p h y s e a l cartilage s u s p e n d e d i n the solution.

B i r d and Thomas

formation

of

apatite

(IS)

crystals

at

found C o unique in preventing concentrations

w h i c h also

the

inhibited

m i n e r a l i z a t i o n of r a c h i t i c cartilage m a t r i x . M A N G A N E S E .

M a n g a n e s e is a n a c t i v a t o r f o r several e n z y m e s s u c h as

b l o o d a n d b o n e phosphatases.

It is a n essential element e v e n t h o u g h there

is n o definite e v i d e n c e that M n d e f i c i e n c y occurs i n m a n . S t e p h a n a n d H a r r i s (180)

n o t e d that d e n t a l caries w a s

somewhat

h i g h w h e n M n was omitted f r o m a synthetic-type diet, a n d reduced w h e n 0 . 1 % M n was a d d e d . W y n n et al Mn

(215)

a d d e d 50, 150, a n d 500 p p m of

to the synthetic t y p e diets of rats a n d n o t e d n o

effect.

caries-reducing

S i m i l a r experiments b y H e n d e r s h o t a n d F o r s a i t h (82)

w i t h the


148

DIETARY

C H E M I C A L S

VS.

D E N T A L

CARIES

M n salt of e t h y l e n e d i a m i n e t e t r a a c e t i c a c i d , M n acetate, or M n versenate w e r e also n e g a t i v e . W h e n 0 . 1 5 m g M n , as t h e sulfate, w a s i n j e c t e d i n t r a p e r i t o n e a l l y d a i l y into rats, t h e caries i n c i d e n c e d i d n o t decrease N a v i a et al. (131) Mn

2 +

s t u d i e d t h e effect of M n C l

2

(100).

supplements ( 2 0 0 0 p p m

) o n a p u r i f i e d c a r i e s - p r o m o t i n g d i e t f e d to rats a n d f o u n d n o effect

o n caries. D r e i z e n et al. (51)

s h o w e d that t h e c o n v e r s i o n of c a r b o h y d r a t e s t o

a c i d residues b y o r a l b a c t e r i a is i n h i b i t e d w h e n M n

2 +

is r e m o v e d b y

c h e l a t i n g c o m p o u n d s . T h e y suggested that t h e M n content of t h e s a l i v a , Downloaded by UNIV OF PITTSBURGH on May 4, 2015 | http://pubs.acs.org Publication Date: June 1, 1970 | doi: 10.1021/ba-1970-0094.ch009

w h i c h a p p r o x i m a t e s 0 . 0 0 5 f t g / m l , c o u l d b e a n i m p o r t a n t factor i n d e n t a l caries a c t i v i t y . B u t t n e r (36)

f o u n d no interaction between M n a n d F

m e t a b o l i s m , e v e n t h o u g h E l T a n n i r ( 5 3 ) h a d suggested that t h e results of a n e p i d e m i o l o g i c a l s u r v e y i n M e c c a i n d i c a t e d that M n c a u s e d a b r o w n c o l o r a t i o n of t h e m o t t l e d e n a m e l i n h u m a n subjects c o n s u m i n g w a t e r containing 2 p p m F . It is e v i d e n t that t h e caries a c t i v i t y of M n is s t i l l u n c l e a r . TIN.

T i n has b e e n s t u d i e d extensively i n recent years, e s p e c i a l l y i n

r e l a t i o n to F . M u h l e r a n d D a y (124)

supplemented the drinking water

of rats w i t h 1 0 p p m S n F a n d f o u n d i t s u p e r i o r to N a F i n r e d u c i n g t h e i n c i d e n c e a n d severity o f d e n t a l caries, w h i l e S n C l

2

h a d no significant

effect. T h e y o b s e r v e d ( 1 2 5 ) a 7 5 % decrease i n caries i n c i d e n c e w h e n i t w a s f e d i n t h e d i e t of rats. T o x i c effects w e r e n o t e d w h e n 5 0 0 p p m w e r e f e d , as s h o w n b y g r o w t h i m p a i r m e n t . essentially w i t h o u t effect (121),

but S n F

s p o n d e d to its fluoride content.

S n gluconate a n d S n C l 2

M u h l e r (122)

were

suggested that t h e m o s t

significant c l i n i c a l effect of t o p i c a l l y - a p p l i e d S n F lesions, a n d M e c k e l (117)

2

h a d a greater effect t h a n c o r r e 2

is exerted o n i n c i p i e n t

i n d i c a t e d that t i n is h e l d v e r y firmly a n d n o

significant losses take p l a c e f o r p e r i o d s u p to 1 1 3 d a y s . T h e w o r k of H o e r m a n et al. (86) w i t h t h e electron p r o b e m i c r o a n a l y s i s i n d i c a t e s that the m e c h a n i s m o f this l o n g persistence o f t i n m i g h t b e its s p e c i a l b i n d i n g p r o p e r t i e s i n " e n r i c h e d " areas of e n a m e l , f r o m w h i c h i t is l e a c h e d s l o w l y over a l o n g p e r i o d o f t i m e . G i s h et al. (62) of K

fluorostannite

t r e a t e d 4 4 2 c h i l d r e n w i t h a 4 % aqueous s o l u t i o n

and found a 5 3 . 7 % reduction i n D M F T a n d a 3 9 . 2 %

reduction i n D M F S .

B r u d e v o l d et al. (29)

r e p o r t e d that S n

w e r e b o t h t a k e n u p w h e n t h e e n a m e l w a s exposed to S n F

2

2 +

and F"

solutions,

especially w h e n the p H was low. ZINC.

47).

Z i n c is present i n b o n e (194)

a n d is q u i t e h i g h i n d e n t i n (46,

Increased levels h a v e b e e n r e p o r t e d i n t h e d e n t a l tissues o f t u b e r c u -

losis patients.

It is d i s t r i b u t e d w i d e l y i n t h e h u m a n b o d y , e s p e c i a l l y i n

the erythrocytes w h e r e i t is a n essential c o m p o n e n t of c a r b o n i c a n h y d r a s e . Z i n c is also a s t r u c t u r a l c o m p o n e n t of t h e phosphatases, t o w h i c h i t c o n -


9.

Effect of

NAVIA

149

Minerals

tributes s t a b i l i t y . Z i n c accumulates o n the surface structures of the t e e t h (31),

b u t occurs i n l o w concentrations i n subsurface m a t e r i a l , a n d shows

a d i s t r i b u t i o n p a t t e r n s i m i l a r to F a n d P b . It is a d i e t a r y essential L i t t l e is k n o w n about the effects of Z n o n d e n t a l caries. (113)

n o t e d a c a r i e s - s t i m u l a t i n g effect w h e n Z n S 0

4

(161).

McClure

( 250 p p m ) w a s f e d

i n the d r i n k i n g w a t e r of rats. H e n d e r s h o t a n d F o r s a i t h (82, 83)

observed

a p p r e c i a b l y l o w e r caries scores w h e n Z n - E D T A w a s f e d to w e a n l i n g m a l e rats, b u t n o significant effect w h e n Z n acetate was g i v e n . Z n s u p p l e ments as Z n C L (2000 p p m Z n ) offered to rats f r o m b i r t h to 60 d a y s of 2 +


age w e r e inert i n terms of s m o o t h surface a n d s u l c a l caries ( 1 3 1 ) . B r o m i n e , w h e n f e d as the b r o m i d e , w a s f o u n d b y Sognnaes

B R O M I N E .

(171)

to increase caries i n rats w h e n f e d d u r i n g t o o t h d e v e l o p m e n t , b u t

to r e d u c e caries s o m e w h a t i f f e d after e r u p t i o n . U s i n g serial a u t o r a d i o g raphy a n d B r , Soremark

(174)

8 2

s h o w e d that b r o m i d e ions enter the

d e n t i n a n d that its a c t i o n m a y v a r y , d e p e n d i n g o n the p e r i o d w h e n administered. IODINE.

I o d i n e (0.005 to 0.002 m g )

rats h a d n o effect o n caries (100).

injected intraperitoneally into

S e v e r a l investigators (49, 114,

152)

h a v e f o u n d that c o m p o u n d s l i k e i o d o a c e t i c a c i d cause a significant r e d u c t i o n i n caries w h e n a d d e d to d r i n k i n g w a t e r .

D a l e and Keyes

o b s e r v e d a n a d d i t i v e effect w h e n i o d o a c e t i c a c i d was g i v e n w i t h U n f o r t u n a t e l y , the L D

5 0

of i o d o a c e t i c a c i d is 116

±

(48)

fluorine.

12 m g / k g b o d y

w e i g h t , w h i c h gives a safety m a r g i n that is too n a r r o w to p e r m i t its a p p l i c a t i o n as p r o p y h l a c t i c agent f o r caries SILICON.

20%

S i l i c o n oils are c a r i o g e n i c w h e n f e d i n the diet at 10 a n d

levels (20),

fluoridation

(110).

b u t s i l i c o f l u o r i d e salts h a v e b e e n u s e d successfully f o r

of w a t e r s u p p l i e s w i t h o u t a n y a p p a r e n t

effectiveness of the

fluoride

i n r e d u c i n g caries.

r e d u c t i o n i n the

N o e v i d e n c e has

been

p r e s e n t e d i n d i c a t i n g that S i is c a r i e s - p r o m o t i n g i n h u m a n s . Caries-Inert Elements.

B A R I U M .

W h e n 0.5 or 1.0%

of B a C L w a s

f e d i n the d i e t of rats, it h a d n o effect o n the d e v e l o p i n g t e e t h or caries s u s c e p t i b i l i t y (168);

h o w e v e r , some r e d u c t i o n i n caries w a s

observed

p o s t - d e v e l o p m e n t a l l y . N o a l t e r a t i o n i n the rate or degree of c a l c i f i c a t i o n i n these a n i m a l s w a s o b s e r v e d . A L U M I N U M .

T h i s element is a b u n d a n t i n the s o i l , a n d is u b i q u i t o u s

i n foods, b u t is not k n o w n to b e essential to h i g h e r a n i m a l s . Its t o x i c i t y is q u i t e l o w . W y n n a n d H a l d i (213)

n o t e d n o effect o n e x p e r i m e n t a l caries d e v e l -

o p m e n t i n rats w h e n 0.16, 2.0, a n d 20 p p m A l w e r e a d d e d to the diet. K r u g e r (100)

f o u n d n o effect o n rat caries w h e n 0.008 a n d 0.025 m g of

A l w e r e f e d as A l acetate. V a n R e e n et al.

S i m i l a r negative results w e r e r e p o r t e d

(200).


by

150

DIETARY

I t appears t o counteract d e n t a l

C H E M I C A L S

fluorosis

D E N T A L

VS.

(201, 203).

CARIES

T h i s effect is

p r o b a b l y a result of decreased d e p o s i t i o n o f F , since t h e F stores i n bones a n d teeth w e r e r e d u c e d b y c o n c u r r e n t A l f e e d i n g . N I C K E L .

N i c k e l is w i d e l y d i s t r i b u t e d i n p l a n t a n d a n i m a l tissues.

It

acts as a n a c t i v a t o r o f several e n z y m e systems, s u c h as arginase a n d trypsin. F o r b e s a n d S m i t h (56)

f o u n d that N i salts exert a m a r k e d i n h i b i t i n g

a c t i o n o n a c i d p r o d u c t i o n i n s a l i v a . H e n d e r s h o t et al. (83) r e p o r t e d that NiCl

2

c a u s e d a n increase o f caries i n rats, t h a t w h e n N i - E D T A w a s g i v e n ,


caries w a s i n h i b i t e d i n m a l e b u t n o t i n f e m a l e rats, a n d t h a t N i acetate h a d n o effect o n either sex. IRON.

T h i s element is i m p o r t a n t t o h e m o g l o b i n f o r m a t i o n a n d is a n

essential element.

T h o u g h n o r m a l l y i t is n o t c o n s i d e r e d a p a r t o f t h e

apatite m o l e c u l e , i t appears essential f o r t h e f o r m a t i o n of t h e orangeb r o w n p i g m e n t that is characteristic of t h e e n a m e l of t h e r o d e n t incisors. M c C l u r e (113)

f e d 2 5 0 a n d 5 0 0 p p m f e r r i c citrate i n t h e d i e t o f rats

a n d n o t e d n o d i s t i n c t effect. T h e same result w a s r e p o r t e d b y W y n n et al. (215)

a n d b y H e n d e r s h o t a n d F o r s a i t h (82) w h e n f e d F e - E D T A . T o r e l l

( 1 9 5 ) suggested t h e p o s s i b i l i t y t h a t f e r r i c solutions m a y establish layers of h y d r o l i z e d f e r r i c precipitates o n e n a m e l w h i c h c o u l d increase caries. P A L A D I U M .

P a l a d i u m c h l o r i d e h a d n o effect o n caries

T I T A N I U M .

V a n R e e n et al. (200)

(210).

f o u n d this element t o b e caries-

inert w h e n tested w i t h t h e N M R I - D rats, a l t h o u g h a s m a l l r e d u c t i o n (about 1 0 % ) was observed w h e n A l , T i , a n d M o were f e d together i n the diet. Experimental

Factors Which Contribute

to the Discrepancy in the

Effect of Minerals on Dental Caries T h e r e v i e w e d results of a large n u m b e r of experiments i n h u m a n s a n d a n i m a l s t o investigate t h e r e l a t i o n s h i p b e t w e e n c e r t a i n trace elements a n d d e n t a l caries are c o n f l i c t i n g . T h e reason f o r this a p p a r e n t c o n f u s i o n is p r i m a r i l y that m a n y factors are i n v o l v e d i n this p r o b l e m .

Experiments

i n w h i c h o n l y some of t h e factors are t a k e n i n t o c o n s i d e r a t i o n c a n n o t b e c o m p a r e d w i t h other experiments w h e r e a different set of factors has been controlled. I n o r d e r to c l a r i f y this p o i n t , i t w o u l d b e of a d v a n t a g e t o r e v i e w b r i e f l y the e x p e r i m e n t a l factors w h i c h influence d e n t a l caries

research

w i t h r e g a r d to trace elements. Species. elements

T h e sensitivity o f a n i m a l species to t h e effect of c e r t a i n

has a w i d e v a r i a t i o n , o w i n g p r i n c i p a l l y t o their

anatomical,

b i o c h e m i c a l , p h y s i o l o g i c a l , a n d m i c r o b i o l o g i c a l differences.

These dif-

ferences are n o t o n l y present

w i t h i n a n i m a l species

(rats,

hamsters,


9.

Effect of

N A V I A

Minerals

151

m o n k e y s ) a n d e v e n strains, b u t also b e t w e e n a n i m a l species a n d h u m a n beings, m a k i n g the e x t r a p o l a t i o n of results a d i f f i c u l t task.

The animal

is a n e x p e r i m e n t a l m o d e l , w h e r e assumptions h a v e to b e m a d e a n d , therefore, results f r o m this t y p e of s t u d y c a n o n l y b e u s e d to u n d e r s t a n d better the p a t h o l o g y of h u m a n caries, a n d not to e x p l a i n i n its entirety

the

h u m a n caries p h e n o m e n a . Route of Administration. E l e m e n t s c a n influence the t o o t h a n d its e n v i r o n m e n t b y e n t e r i n g the o r g a n i s m t h r o u g h diet, w a t e r , air, or cage environment.

E x p e r i m e n t a l l y , elements

also c a n b e

administered


i n j e c t i o n a n d b y t o p i c a l a p p l i c a t i o n s o n the t o o t h surface

(73).

effectiveness of these different routes i n f a c i l i t a t i n g the effect of

by The the

c h e m i c a l agent is d e p e n d e n t o n the a v a i l a b i l i t y of the c o m p o u n d a n d its p a r t i c u l a r m e c h a n i s m of a c t i o n o n the tooth—i.e., i n c o r p o r a t i o n i n t o e n a m e l , o n the p l a q u e , or surface a d s o r p t i o n , etc. T h e effects of elements, therefore,

c a n b e c o m p a r e d o n l y w h e n the f o r m of a d m i n i s t r a t i o n is

t h r o u g h e q u a l routes. Time (Age)

of Administration. T h e t i m e at w h i c h the element is

g i v e n has a p r o f o u n d influence w i t h r e g a r d to the d e v e l o p m e n t of the a n i m a l a n d the stage of d e v e l o p m e n t of the tooth. C e r t a i n elements m a y e x h i b i t t o x i c properties w h e n f e d to y o u n g i m m a t u r e a n i m a l s a n d , therefore, i n h i b i t t h e i r g r o w t h a n d d e v e l o p m e n t , the result b e i n g a sick a n d a b n o r m a l a n i m a l w i t h u n p h y s i o l o g i c a l responses.

T h e stage of d e v e l o p -

m e n t of the t o o t h is a n e v e n m o r e i m p o r t a n t factor, f o r i f the

element

is to b e i n c o r p o r a t e d or a d s o r b e d b y the t o o t h , this c a n take p l a c e o n l y at the i n i t i a l stages of d e v e l o p m e n t or e r u p t i o n a n d not w h e n the e n a m e l m i n e r a l has m a t u r e d a n d lost its r e a c t i v i t y

(133).

Chemistry and Availability of the Mineral Compound. T h e c h e m i c a l structure, v a l e n c e , a n d s o l u b i l i t y are f u n d a m e n t a l factors w h i c h also d e t e r m i n e the a c t i v i t y of the element w i t h r e g a r d to d e n t a l caries.

The

c h e m i c a l properties of a c o m p o u n d b e i n g tested influence t h e i n t e s t i n a l a b s o r p t i o n , the o r a l a n d i n t e s t i n a l flora, a n d the d i r e c t l o c a l u p t a k e b y the t o o t h or p l a q u e .

E x p e r i m e n t s , therefore, e v e n t h o u g h t h e y m a y use

s i m i l a r levels of a c e r t a i n element, are not c o m p a r a b l e i f the c h e m i c a l structure of the c o m p o u n d is different. E x a m p l e s h a v e b e e n c i t e d w h e r e a c h e m i c a l f o r m is effective at a p a r t i c u l a r t o o t h d e v e l o p m e n t stage a n d not at another later stage. Requirement and Toxicity Levels: Biological Reserves. T r a c e

ele-

ments p l a y a p a r t i n m a n y b i o l o g i c a l reactions, a n d some are d e f i n i t e l y essential n u t r i e n t s ; n o n o r m a l d e v e l o p m e n t c a n take p l a c e i n t h e i r absence.

The

amounts

r e q u i r e d are u s u a l l y e x t r e m e l y

v e r y d i f f i c u l t to investigate tions of elements. exists

about the

s m a l l , a n d it is

the p a r t p l a y e d b y s u c h l o w

concentra-

It is not at a l l s u r p r i s i n g , therefore, that u n c e r t a i n t y significance

of some

trace elements

with regard


to

152

DIETARY

nutrition

a n d dental

health.

Another

C H E M I C A L S

problem

VS.

that

D E N T A L

CARIES

confronts

the

investigator is that a l l l i v i n g matter contains trace elements, a n d t h e y store t h e m i n organs s u c h as t h e l i v e r i n vertebrates o r other structures i n the l o w e r f o r m s . T h e e n d result is that i t is q u i t e i m p o s s i b l e to d e p l e t e the

organisms

b i o l o g i c a l reserves

o f nutrients

e n o u g h to observe

a

clear d e n t a l effect o r n u t r i t i o n a l s y m p t o m s o f a trace element d e f i c i e n c y . T h e l o w r e q u i r e m e n t s o f these trace elements

together w i t h t h e

h i g h t o x i c i t y e x h i b i t e d b y m a n y elements f u r t h e r c o m p l i c a t e s t h e i r investigations, f o r s l i g h t l y h i g h e r levels u s u a l l y b r i n g a b o u t t o x i c effects w h i c h Downloaded by UNIV OF PITTSBURGH on May 4, 2015 | http://pubs.acs.org Publication Date: June 1, 1970 | doi: 10.1021/ba-1970-0094.ch009

influence t h e p h y s i o l o g i c a l status a n d t h e r e b y obscure t h e i n t e r p r e t a t i o n of experiments, as i s t h e case w i t h s e l e n i u m or m o l y b d e n u m . Type of Diet. I n d e n t a l caries research, t h e t y p e o f d i e t u s e d determ i n e s to a large extent t h e a m o u n t , t y p e , a n d d i s t r i b u t i o n of carious lesions i n t h e m o l a r s . N u t r i t i o n a l l y , d i e t determines t h e degree o f w e l l being a n d normal development a n d maintenance

of e x p e r i m e n t a l a n i -

m a l s , b u t i n caries research, c e r t a i n diets h a v e b u i l t - i n i m b a l a n c e s , m a i n l y i n t h e amounts of p r o t e i n a n d m i n e r a l s w h i c h are responsible f o r its c a r i o g e n i c i t y . C a r i e s - p r o m o t i n g diets, to b e effective, h a v e to a l l o w t h e d e v e l o p m e n t of different types o f lesions at the same t i m e that t h e y satisfy the r e q u i r e m e n t s f o r n o r m a l d e v e l o p m e n t .

Diets c a n b e d i v i d e d into

n a t u r a l , p u r i f i e d , a n d c h e m i c a l l y d e f i n e d (130).

W o r k w i t h trace elements

requires t h e use of p u r i f i e d diets m a d e u p of a c a r b o h y d r a t e a n d p r o t e i n source p l u s some o i l a n d a salt a n d v i t a m i n m i x t u r e . T h i s t y p e o f d i e t has the a d v a n t a g e that its c o m p o s i t i o n c a n b e c o n t r o l l e d a n d the trace elements c a n b e k e p t constant, a v o i d i n g t h e

fluctuations

d u e to variations

i n t h e c o m p o s i t i o n of p l a n t f o o d ingredients u s e d i n n a t u r a l diets. c o m p o s i t i o n , f e e d i n g f r e q u e n c y , p h y s i c a l structure, a n d o r a l

Diet

clearance

are i m p o r t a n t factors i n t h e c o n d u c t of e x p e r i m e n t a l caries research. Interferences from Components of Diet.

T h e n a t u r e of the c a r i o -

g e n i c d i e t influences t h e a v a i l a b i l i t y of trace elements f r o m f o o d m a t e rials, t h e storage of those elements i n t h e tissues, t h e i r i n c o r p o r a t i o n i n t o t h e i r f u n c t i o n a l positions i n t h e c e l l a n d , finally, t h e i r excretion.

The

m e t a b o l i s m of c o p p e r is m a r k e d l y affected b y m o l y b d e n u m a n d that of m o l y b d e n u m b y t h e levels of i n o r g a n i c sulfate i n t h e diet.

T h e zinc

r e q u i r e m e n t a p p a r e n t l y is i n c r e a s e d w h e n i s o l a t e d soy-bean p r o t e i n is u s e d i n s t e a d of casein as a p r o t e i n source i n p u r i f i e d diets. P h y t i c a c i d influences t h e u p t a k e of c a l c i u m a n d i r o n i n c e r t a i n species, s u c h as the p i g . D i e t s u s e d i n caries research s h o u l d b e s t u d i e d c a r e f u l l y a n d screened o u t f o r possible interferences a n d m i n e r a l interactions w h i c h m a y b r i n g a b o u t a d d i t i o n a l a n d u n k n o w n sources of v a r i a t i o n i n t h e experiments. Trace Elements or Contaminants. T h e v e r y l o w r e q u i r e m e n t of trace elements a n d t h e u b i q u i t o u s presence o f trace elements i n n a t u r e d e m a n d


9.

N A V I A

Effect of

Minerals

153

a r i g i d c o n t r o l of the e n v i r o n m e n t s u r r o u n d i n g e x p e r i m e n t a l a n i m a l s u s e d i n caries research.

T r a c e e l e m e n t c o n t a m i n a n t s c a n c o m e f r o m the cage,

e s p e c i a l l y i f these are g a l v a n i z e d or h a v e m e t a l parts to w h i c h t h e a n i m a l s h a v e r e a d y access; the w a t e r , i f this is n o t c a r e f u l l y d i s t i l l e d a n d stored i n tanks m a d e of i n e r t m a t e r i a l s ; d i e t i n g r e d i e n t s ; a n d the a t m o s p h e r e , i f a i r is n o t filtered a n d c o n d i t i o n e d to p r o p e r t e m p e r a t u r e a n d h u m i d i t y . Methods of Analysis and Caries Evaluation. T r a c e e l e m e n t

content

of diets a n d w a t e r s h o u l d b e a n a l y z e d c a r e f u l l y i n o r d e r to s t a n d a r d i z e the e x p e r i m e n t a l c o n d i t i o n s . C e r t a i n organs, besides teeth a n d other o r a l


structures, s h o u l d b e dissected a n d a n a l y z e d f o r trace elements i n o r d e r to u n d e r s t a n d t h e i r effects o n the o r g a n i s m a n d , i n p a r t i c u l a r , o n the d e n t a l structures. T h e l o w levels of elements i n v o l v e d a n d the p o s s i b i l i t y of c o n t a m i n a t i o n d u r i n g p r e p a r a t i o n of samples f o r analysis r e q u i r e t h e use of p h y s i c a l m e t h o d s s u c h as n e u t r o n a c t i v a t i n g analysis a n d

electron

p r o b e m i c r o a n a l y s i s to u n d e r s t a n d their d i s t r i b u t i o n i n m i c r o s t r u c t u r e s . R e c e n d y , the e l e c t r o n p r o b e m e t h o d of analysis has b e e n greatly i m p r o v e d , e n a b l i n g the researcher to scan a t o o t h structure a n d d e t e r m i n e levels of elements s u c h as P a n d C a as w e l l as l i g h t e r elements i n 1 - m i c r o n areas. I n cases w h e r e this is n o t feasible, s p e c t r o g r a p h i c analysis or t h e a t o m i c a b s o r p t i o n s p e c t r o p h o t o m e t r y b e c o m e the m e t h o d s of c h o i c e , f o r t h e y are a b l e to detect elements i n parts p e r m i l l i o n levels. L a r g e n u m bers of analyses c a n be c a r r i e d o u t w i t h the latter m e t h o d , w h i l e the s p e c t r o g r a p h i c p r o c e d u r e is u s e f u l i n that several elements c a n b e assayed readily i n a sample. T h e m e t h o d u s e d i n the e s t i m a t i o n of caries extent a n d severity is i m p o r t a n t , f o r it s h o u l d b e a d e q u a t e f o r t h e t y p e of l e s i o n b e i n g f o r m e d b y the c a r i o g e n i c d i e t u s e d a n d the d u r a t i o n of the experiment.

Caries

s c o r i n g m e t h o d s differ i n t h e i r r e p r o d u c i b i l i t y a n d i n t h e i r specificities, a n d c a r e f u l t h o u g h t s h o u l d b e g i v e n to t h e c h o i c e of m e t h o d a n d to t h e c o m p a r i s o n of e x p e r i m e n t a l results o b t a i n e d i n the different caries s c o r i n g procedures. O t h e r m e t h o d s are u s e d i n caries research, s u c h as hardness tests, s o l u b i l i t y tests, d y e p e n e t r a t i o n tests, etc., w h i c h are u s e d to evaluate the effects of trace elements o n t o o t h structure, b u t t h e y a l l r e q u i r e a h i g h degree of s t a n d a r d i z a t i o n i n o r d e r to o b t a i n m e a n i n g f u l a n d c o m p a r a b l e results.

T h e s e in vitro m o d e l s s h o u l d b e c a u t i o u s l y e v a l u a t e d , f o r t h e y

m a y b e t o t a l l y u n r e l a t e d to the in vivo p h e n o m e n a . Experimental Design. A m u l t i p l i c i t y of factors affect the results of d e n t a l caries experiments a n d interact

between them, p r e c l u d i n g the

p o s s i b i l i t y of o b t a i n i n g m e a n i n g f u l results f r o m experiments w h e r e one of the factors is v a r i e d a n d the rest are m a i n t a i n e d constant (65,

98).

T h e r e f o r e , i n the d e s i g n of experiments i n w h i c h m a n y factors

are

i n v o l v e d , the s o - c a l l e d f a c t o r i a l e x p e r i m e n t (i.e., a l l c o m b i n a t i o n s of a l l


154

DIETARY CHEMICALS VS. DENTAL

CARIES

levels of all factors) or fractional factorials in which only some of the factors are statistically evaluated w i l l allow estimates of existence of interactions. Factorial analysis has the disadvantage that as the number of factors increases, the experiment becomes extremely large. F o r i n stance, for 6 factors at only two levels, the factorial experiment requires 2 = 64 trials. Statistical designs have been described for reducing the number of runs in large-scale fractional replication studies which enable the experimenter to draw up schedules which permit the examination of results at various stages of the research work. The selection of subsequent trials can be made as the results of the previous trials are obtained. Experimental designs of this type w i l l make dental caries research experiments fruitful and effective.


6

Conclusion The results of an exhaustive literature review on the effect of trace elements i n dental caries has been presented. Epidemiological data as well as experimental data obtained with animal studies indicate that the mineral portion of foods influences the prevalance of dental caries. Trace elements may act as "bone-seeking" elements and accumulate in the skeleton and teeth to modify their development and composition as well as their chemical-physical properties. This influence, i n the case of those elements in high concentration in surface enamel, may extend into the plaque, the oral flora, and the surrounding environment of the tooth. When the literature is evaluated, a highly tentative classification can be made of the type of effect shown by trace elements with regard to dental caries, in spite of the fact that a large number of experiments present conflicting results. The source of confusion i n these observations can be traced to the multiplicity of factors which enter into dental caries research and its relation to mineral nutrition. Research work in which these factors are taken into consideration should be attempted in order to clarify the influence of mineral elements on dental caries.

Literature Cited (1) Adler, P., Dent. Stomatol. 1965, 15, 96-110. (2) Adler, P., Odontol. Rev. 1957, 8, 52. (3) Adler, P., Straub, J., Acta Med. Acad. Sci. Hung. 1953, 4, 221-227.



9.

ΝΑVIA

Effect of Minerals

155

(4) Andersen, C. Α., Hasler, M . F., "X-Ray Optics and Microanalysis," p. 310, Herman, Paris, 1966. (5) Anderson, R. J., Brit. Dental J. 1966, 120, 271-275. (6) Anderson, R. S., Proc. ORCA Conf. Advan. Fluorine Res. and Dental Caries Prevent., 11th, 1965, 3, 165-169. (7) Asgar, K., J. Dental Res. 1956, 35, 742-748. (8) Aslander, Α., "Dental Caries: The Bone Meal Method and the Cariogenic Properties of Sugar," Royal Institute of Technology, Division of Agriculture, Stockholm, Sweden, 1960. (9) Bachra, Β. N . , Trautz, O. R., Simon, O. L . , Arch. Oral Biol. 1965, 10, 731—738. (10) Banks, S. O., Bhaskar, S. N . , Weinmann, J. P., Arch. Pathol. 1951, 51, 19-29. (11) Battistone, G. C., Feldman, M . H . , Reba, R. C., Arch. Oral Biol. 1967, 12, 1115-1122. (12) Baume, L . J., Mayer, J., J. Dental Res. 1966, 45, 726-774. (13) Becks, H . , Furuta, W . J., J. Am. Dental Assoc. 1941, 28, 1083-1088. (14) Bibby, B. G., J. Am. Med. Assoc. 1961, 177, 316-321. (15) Bird, E . D., Thomas, W . C., Proc. Soc. Exptl. Biol. Med. 1963, 112, 640-643. (16) Birks, L . S., "Electron Probe Microanalysis," Wiley, New York, 1963. (17) Bowen, W . H., Arch. Oral Biol. 1968, 13, 713-714. (18) Bowen, W . H . , Eastoe, J. E., Caries Res. 1967, 1, 130-136. (19) Boyde, Α., Switsur, V . R., Fearnhead, R. S., J. Ultrastruct. Res. 1961, 5, 201-207. (20) Boyers, C. L . , Shaw, J. H . , Rosenthal, E., Giordana, R., J. Dental Res. 1963, 42, 1517. (21) Brekhus, P. J., Armstrong, W . D., J. Am. Dental Assoc. 1936, 23, 14591470. (22) Briner, W. W., Rosen, S., Arch. Oral Biol. 1967, 12, 1077-1084. (23) Briner, W. W., Rosen, S., Calcified Tissue Res. 1968, 2, 60-66. (24) Brudevold, F., "The Chemistry and Prevention of Dental Caries," p. 32, R. F. Sognnase, Ed., C. C. Thomas, Springfield, Ill., 1962. (25) Brudevold, F., Messer, A. C., J. Dental Res. 1961, 40, 728 (Abstr.). (26) Brudevold, F., Steadman, L . T., J. Dental Res. 1955, 34, 209-216. (27) Ibid., 1956, 35, 430-437. (28) Ibid., 1956, 35, 749-752 (29) Brudevold, F., Steadman, L . T., Gardner, D . E., Rowley, J., Little, M . F., J. Am. Dental Assoc. 1956, 53, 159-164. (30) Brudevold, F., Steadman, L . T., Smith, F. Α., Ann. Ν. Y. Acad. Sci. 1960, 85, 110-132. (31) Brudevold, F., Steadman, L . T., Spinelli, Μ. Α., Amdur, Β. H . , Gron, P., Arch. Oral Biol. 1963, 8, 135-144. (32) Bryant, F. J., Henderson, E . H . , Holgate, W., Brit. Dental J. 1960, 108, 291-294. (33) Butler, F. E., Nature 1961, 189, 848-849. (34) Buttner, W., Advan. Fluorine Res. Dental Caries Prevent. 1965, 3, 19-30. (35) Buttner, W., Arch. Oral Biol. Spec. Suppl. 1961, 6, 40-49. (36) Buttner, W., J. Dental Res. 1963, 42, 453-460. (37) Cadell, P. B., Cousins, F. B., Nature 1960, 185, 863-864. (38) Calonius, P. Ε. B., Visapaa, Α., Arch. Oral Biol. 1965, 10, 9-13. (39) Campbell, W. J., Brown, J. D., Anal. Chem. 1968, 40, 346R-375R. (40) Claycomb, C. K., Sorenson, F. M . , Gatewood, D. C., Jump, Ε. B., Weaver, M . E., J. Dental Res. 1961, 40, 504-510.



156

DIETARY C H E M I C A L S VS. DENTAL CARIES

(41) Claycomb, C. K., Summers, G. W., Jump, E . B., J. Dental Res. 1965, 44, 826. (42) Constant, M . A., Phillips, P. H., Elvehjem, C. A., J. Nutr. 1952, 46, 271. (43) Constant, M . A., Sievert, H . W., Phillips, P. H., Elvehjem, C. A., J. Nutr. 1954, 53, 17-27. (44) Ibid., 1954, 53, 29-41. (45) Crane, D . B., J. Dental Res. 1960, 39, 704. (46) Cruickshank, D . B., Biochem. J. 1949, 44, 299. (47) Cruickshank, D . B., Brit. Dental J. 1940, 68, 257-271. (48) Dale, P. P., Keyes, P. H . , J. Dental Res. 1945, 24, 194. (49) Dale, P. P., Powell, V. H . , J. Dental Res. 1943, 22, 33. (50) Deakins, M., J. Dental Res. 1942, 21, 429-435. (51) Dreizen, S., Niedermeier, W., Dreizen, J. G., Spies, T. D., J. Dental Res. 1958, 37, 1149-1156. (52) Dreizen, S., Spies, H . A., Jr., Spies, T. D., J. Dental Res. 1952, 31, 137142. (53) E l Tannir, M . D., Am. J. Public Health 1959, 49, 45. (54) English, J. A., J. Dental Res. 1949, 28, 172-194. (55) Ericcson, Y., Acta Odontol. Scand. 1954, 11, 167. (56) Forbes, J. C., Smith, J. D., J. Dental Res. 1952, 31, 129. (57) Francis, M. D., Briner, W . W., Arch. Oral Biol. 1966, 11, 349-354. (58) Frank, R. M., Capitant, M . , Goni, J., J. Dental Res. 1966, 45, 672-682. (59) Frazier, P. D., Arch. Oral Biol. 1967, 12, 25-33. (60) Geyer, C. F., J. Dental Res. 1953, 32, 590-595. (61) Ginn, J. T., Volker, J. F., Proc. Soc. Exptl. Biol. Med. 1944, 57, 189. (62) Gish, C. W., Muhler, J. C., Howell, C. L., J. Dental Res. 1957, 36, 780. (63) Goldenberg, H . , Sobel, A. E., Proc. Soc. Exptl. Biol. Med. 1952, 81, 695-698. (64) Gustafson, G., Stelling, E., Brunius, E., Acta Odontol. Scand. 1963, 21, 297-308. (65) Guzman, M . A., "The Art and Science of Dental Caries Research," p. 131-149, Academic, New York, 1968. (66) Hadjimarkos, D . M., Brit. Dental J. 1967, 123, 201-202. (67) Hadjimarkos, D . M., Experientia 1967, 23, 930-932. (68) Hadjimarkos, D . M., Bonhorst, C. W., J. Pediat. 1958, 52, 274-278. (69) Hadjimarkos, D . M., Bonhorst, C. W., Nature 1962, 193, 177-178. (70) Hadjimarkos, D . M . , Bonhorst, C. W., Oral Surg. Oral Med. Oral Pathol. 1959, 12, 113-116. (71) Hadjimarkos, D . M . , Starvick, C. A., Remmert, L . F., J. Pediat. 1952, 40, 451-455. (72) Hardwick, J. L., "Caries Resistant Teeth," p. 222-237, Ciba Foundation Symp., 1965. (73) Harris, R. S., Navia, J. M . , Ann. N.Y. Acad. Sci. 1968, 153, 240-257. (74) Harris, R. S., Nizel, A. E., Intern. Congr. Nutr., 4th, 1957, p. 195. (75) Harris, R. S., Nizel, A. E., J. Dental Res. 1959, 38, 1142-1147. (76) Head, J., J. Am. Med. Assoc. 1912, 59, 2118-2122. (77) Hein, J. W., "Advances in Experimental Caries Research," p. 197-222, G. R. Sognnaes, Ed., Am. Assoc. Advan. Sci., Washington, D . C., 1955. (78) Hein, J. W., J. Dental Res. 1953, 32, 654. (79) Hein, J. W., Quigley, G. A., Marcussen, H . , J. Dental Res. 1958, 37, 34. (80) Hein, J. W., Shafer, W . C., J. Dental Res. 1951, 30, 510. (81) Hein, J. W., Wisotzky, S., J. Dental Res. 1955, 34, 756. (82) Hendershot, L . C., Forsaith, J., J. Dental Res. 1958, 37, 32-33. (83) Hendershot, L . C., Monselll, E., Forsaith, J., "Metal-Binding in Medicine," pp. 306-311, J. J. Seven and A. L. Johnson, Eds., Lippincott, Philadelphia, 1960.



9.

NAVIA

Effect of Minerals

157

(84) Herrmann, M . , Rozeik, F., Deut. Zahnaerztl. Z. 1962, 17, 880-885. (85) Hewat, R. E . T., Eastcott, D . F., "Dental Caries in New Zealand," Medical Research Council of New Zealand Publication, 1955. (86) Hoerman, K. C., Klima, J. E . , Birks, L . S., Nagel, D . S., Ludwick, W . E . , Lyon, H . W., J. Am. Dental Assoc. 1966, 73, 1301-1305. (87) Holgate, W., Mole, R. H . , Vaughan, J., Nature 1958, 182, 1294-1295. (88) Irving, J. T., J. Physiol. 1940, 99, 8-17. (89) Issac, S., Brudevold, F., J. Dental Res. 1957, 36, 753-758. (90) Jenkins, G. N., Brit. Dental J. 1967, 122, 435-441. (91) Ibid., 1967, 122, 500-503. (92) Ibid., 1967, 122, 545-550. (93) Johansson, B., J. Dental Res. 1965, 44, 64-70. (94) Johansen, E., Hein, J. W., J. Dental Res. 1953, 32, 703. (95) Johnson, A. R., Singer, L., Arch. Oral Biol. 1967, 12, 389-399. (96) Keyes, P. H., J. Dental Res. 1956, 35, 95-101. (97) Kinkel, H . J., Cremer, H . D., J. Dental Res. 1960, 39, 640. (98) Konig, K. G., "The Art and Science of Dental Caries Research," pp. 201-230, Academic, New York, 1968. (99) Kruger, B. J., J. Dental Res. 1966, 45, 714-725. (100) Kruger, B. J., Univ. Queensland Papers, Dept. of Dentistry 1959, 1, 1-28. (101) Landing, B. H . , Lahey, W . K., Schubert, J., Spinanger, J., J. Dental Res. 1957, 36, 750. (102) Leicester, H . M., J. Dental Res. 1946, 25, 337. (103) Leicester, H . M., Thomassen, P. R., Nicholas, L . W., J. Dental Res. 1954, 33, 670. (104) Little, M . F., Brudevold, F., J. Dental Res. 1958, 37, 991-1000. (105) Lobene, R. R., Burnett, C. W., J. Dental Res. 1954, 33, 487. (106) Losee, F. F., Am. Assoc. Adv. Sci., Publ. 81, 1964, 41-54. (107) Ludwig, T. G., Healy, W. B., Losee, F. L . , Nature 1960, 186, 695-696. (108) Ludwig, T. G., Malthus, R. S., Healy, W . B., Nature 1962, 194, 456458. (106) Losee, F. L., Am. Assoc. Adv. Sci., Publ. 81, 1964, 41-54. 8-11. (110) Lundquist, C., J. Dental Res. 1951, 30, 203. (111) Malthus, R. S., Ludwig, T. G., Healy, W . B., N.Z. Dental J. 1964, 60, 291-296. (112) Maynard, E . A., Downs, W . L . , Scott, J. K., Federation Proc. 1950, 9, 338. (113) McClure, F. J., J. Dental Res. 1948, 27, 34-40. (114) McClure, F. J., Arnold, F. A., J. Dental Res. 1941, 20, 97. (115) McClure, F. J., McCann, H . G., Arch. Oral Biol. 1960, 2, 151-161. (116) McDonald, J. B., "Chemistry and Prevention of Dental Caries," p. 89, R. F. Sognnaes, Ed., C. C. Thomas, Springfield, Ill., 1962. (117) Meckel, A. H . , J. Dental Res. 1962, 41, 1104. (118) Miller, C. D., J. Nutr. 1963, 80, 217-222. (119) Moxon, A. L., Rhian, M., Physiol. Rev. 1943, 23, 305. (120) Muhlemann, H . R., Konig, K. G., Helv. Odontol. Acta 1964, 8, Suppl. 1, 79-81. (121) Muhler, J. C., J. Dental Res. 1957, 36, 787-794. (122) Muhler, J. C., J. Indiana Dental Assoc. 1960, 39, 42. (123) Muhler, J. C., Bixer, D., Shafer, W. C., Proc. Soc. Exptl. Biol. Med. 1956, 93, 328. (124) Muhler, J. C., Day, H . G., J. Am. Dental Assoc. 1950, 41, 528. (125) Muhler, J. C., Day, H . G., J. Nutr. 1951, 44, 413. (126) Muhler, J. C., Shafer, W . C., J. Dental Res. 1957, 36, 895-896.


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


(127) (128) (129) (130)

Muhler, J. C., Shafer, W . C., Science 1954, 119, 687. Munch, J., Odontol. Rev. 1957, 8, 52. Myrback, K., Z. Physiol. Chem. 1926, 159, 1-21. Navia, J. M . , "The Art and Science of Dental Caries Research," pp. 245-255, Academic, New York, 1968. (131) Navia, J. M . , Cagnone, L . D., Lopez, H . , Harris, R. S., Proc. Intern. Assoc. Dental Res., 46th, 1968, p. 128. (132) Navia, J. M . , Henry, C. H . , Lopez, H . , Harris, R. S., Federation Proc. 1967, 26, 415. (133) Navia, J. M . , Lopez, H . , Harris, R. S., Arch. Oral Biol. 1968, 13, 779786. (134) Navia, J. M . , Lopez, H . , Harris, R. S., J. Nutr. 1969, 97, 133-140. (135) Navia, J. M . , Menaker, L . , Seltzer, J., Harris, R. S., Federation Proc. 1968, 27, 676. (136) Neuman, W . F., Neuman, M . W., "The Chemical Dynamics of Bone Mineral," University of Chicago Press, Chicago, Ill., 1958. (137) Nixon, G. S., Livingstone, H . D., Smith, H . , Arch. Oral Biol. 1966, 11, 247-252. (138) Nixon, G. S., Livingstone, H . D., Smith, H . , Caries Res. 1967, 1, 327332. (139) Nixon, G. S., Smith, H . , J. Dental Res. 1960, 39, 514-516. (140) Ibid., 1962, 41, 1013-1016. (141) Nizel, A. E., Bibby, B. G., J. Am. Dental Assoc. 1944, 31, 1619-1626. (142) Nizel, A. E . , Harris, R. S., Arch. Biochem. 1950, 26, 155-157. (143) Nizel, A. E . , Harris, R. S., J. Dental Res. 1955, 34, 513-515. (144) Nizel, A. E . , Harris, R. S., N. Eng. J. Med. 1951, 244, 361-362. (145) Parizek, J., J. Endocrinol. 1957, 15, 56. (146) Parizek, J., Nature 1956, 177, 1036. (147) Parma, C., Danek, J., Hanusova, N . , Cs. Stomatol. 1952, 52, 150. (148) Picard, J., Cartier, P., Carties, Α., C.R. Soc. Biol. 1952, 146, 1488-1491. (149) Pigman, W., Cueto, H . , Baugh, D., J. Dental Res. 1964, 43, Suppl. No. 6, 1187-1195. (150) Pindborg, Ε. V., Pindborg, J. J., Plum, C. M . , Acta Pharmacol. Toxicol. 1946, 2, 302. (151) Pindborg, J. J., Oral Surg., Oral Med., Oral Pathol. 1953, 6, 780. (152) Powell, V. H . , Dale, P. O., J. Dental Res. 1943, 22, 257. (153) Ritchie, D . B., Nature 1961, 190, 456-458. (154) Rosser, H . , Boyde, Α., Stewart, A. D . G., Arch. Oral Biol. 1967, 12, 431-440. (155) Rozeik, F., Cramer, H . D., Hannover, R., Deut. Zahnaerztl. Z. 1956, 11, 1104-1109. (156) Russell, A. L., in "Environmental Variables in Oral Disease," pp. 21-39, Am. Assoc. Advan. Sci., Washington, D . C., 1966. (157) Russell, A. L., J. Dental Res. 1963, 42, 233-244. (158) Rygh, O., Bull. Soc. Chem. Biol. 1949, 31, 1052. (159) Rygh, O., Den Norske Tannloegeforeningst Idenc. 1950, 60, 1-19. (160) Rygh, O., Research 1949, 2, 443. (161) Ibid., 1950, 3, 193-194. (162) Schwarz, K., Foltz, C. M., J. Am. Chem. Soc. 1957, 79, 3292. (163) Schwarz, K., Cited in Nutr. Rev. 1958, 16, 149, 174. (164) Schwarz, K., Vitamins Hormones 1962, 20, 463-484. (165) Scott, D . B., Kaplan, H . , Wyckoff, R. W . O., J. Dental Res. 1949, 28, 31-47. (166) Scrimshaw, N. S., Taylor, C. E., Gordon, J. E . , Am. J. Med. Sci. 1959, 237, 367-403. (167) Shaw, J. Η., N.Y. State Dental J. 1950, 16, 503.


9.

NAVIA

(168) (169) (170) (171) (172) (173) (174) (175) (176) (177) (178)


(179) (180) (181) (182) (183) (184) (185) (186) (187) (188) (189) (190) (191) (192) (193) (194) (195) (196) (197) (198) (199) (200) (201) (202) (203) (204) (205) (206) (207) (208) (209) (210) (211)

Effect of Minerals

159

Shaw, J. H., Griffiths, D., Arch. Oral Biol. 1961, 5, 301-327. Sherman, B. S., Sobel, A. E., J. Dental Res. 1965, 44, 454. Smith, M. I., Westfall, Β. B., Public Health Repts. 1937, 52, 1375. Sognnaes, R. F., J. Nutr. 1949, 39, 147-157. Sognnaes, R. F., Shaw, J. H . , J. Dental Res. 1953, 32, 685. Sognnaes, R. F., Shaw, J. H . , J. Nutr. 1954, 53, 195-206. Soremark, R., Acta Radiol. Suppl. 1960, 190, 1. Soremark, R., Lundberg, M . , Acta Odontol. Scand. 1964, 22, 255. Soremark, R., Samsahl, K., Arch. Oral Biol. 1961, 6, 275-283. Speirs, R. L . , Caries Res. 1967, 1, 15-31. Steadman, L . T., Brudevold, F., Smith, F. Α., J. Am. Dental Assoc. 1958, 57, 340. Steadman, L . T., Brudevold, F., Smith, F. A., Gardner, D . E., Little, M . F., J. Dental Res. 1959, 33, 285-292. Stephan, R. M., Harris, M. R., J. Dental Res. 1953, 32, 708. Stookey, G. K., Muhler, J. C., J. Dental Res. 1960, 39, 671. Stookey, G. K., Roberts, R. A., Muhler, J. C., Proc. Soc. Exptl. Biol. 1962, 109, 702-706. Stralfors, A., Arch. Oral Biol. 1966, 11, 149-161. Ibid., 1966, 11, 323-328. Ibid., 1966, 11, 609-615. Ibid., 1967, 12, 1375-1385. Suga, S., Gustafson, G., Arch. Oral Biol. Suppl. 1962, 223-244. Swift, P., Brit. Dental J. 1967, 123, 326-327. Takuma, S., Katagiri, S., Ozasa, S., J. Electron Microscopy 1966, 15, 86-89. Tank, G., Storvick, C. A., J. Dental Res. 1960, 39, 473-488. Tempestini, O., Pappalardo, G., Panminerva Med. 1960, 38, 344. Thomassen, P. R., Leicester, H. M . , J. Dental Res. 1959, 38, 670. Ibid., 1964, 43, 346-352. Tipton, I. H . , Foland, W . D., Bobb, F. C., McCorble, W . C., Oak Ridge National Lab. USAEC Report CF-53-8-4, 1953. Torell, P., Odontol. Tidsk. 1956, 64, 165-183. Toth, K., Acta Med. Hung. 1954, 6, 493-500. Tousimis, A. J., Am. J. Med. Electronics 1966, 5, 15-20. Tousimis, A. J., "X-Ray Optics and X-Ray Microanalysis," pp. 539-557, Academic, New York, 1963. Van Reen, R., Ostrom, C. H . , Berzinskas, V . J., Arch. Oral Biol. 1962, 7, 351-359. Van Reen, R., Ostrom, C. A., Berzinskas, V. J., Helv. Odontol. Acta 1967, 11, 53-59. Venkataramanan, K., Krishnaswany, N . , Indian J. Med. Res. 1949, 37, 277. Von der Fehr, F., Advan. Fluorine Res. Dental Caries Prevent. 1965, 3, 83-98. Wadhwani, T. K., J. Indian Inst. Sci. 1954, 36, 64. Wentz, J., J. Dental Res. 1955, 34, 735. Wessinger, G. D., Weinmann, J. P., Am. J. Physiol. 1943, 139, 233-238. Wheatcroft, M . G., English, J. A., Schlack, C. A., J. Dental Res. 1951, 30, 523. Widdowson, E . M . , McCance, R. A., Spray, C. M . , Clin. Sci. 1951, 10, 113-118. Winiker, M . , Odontol. Rev. 1957, 8, 42. Wisotzky, J., Hein, J. W., IADR Meeting, 34th, 1956, No. 36. Wisotzky, J., Hein, J. W., J. Am. Dental Assoc. 1958, 57, 797. Wisotzky, J., Hein, J. W., J. Dental Res. 1955, 34, 735.


160

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(212) (213) (214) (215)

Ibid., 1955, 34, 768. Wynn, W., Haldi, J., J. Nutr. 1954, 54, 285-290. Wynn, W., Haldi, J., Law, M . L . , J. Dental Res. 1960, 39, 153-157. Wynn, W., Haldi, J., Law, M. L., Bentley, K. D . , J. Dental Res. 1958, 37, 33. (216) Yaeger, J. A., J. Dental Res. 1963, 42, 1178-1182. (217) Zipkin, I., "Art and Science of Dental Caries Research," pp. 29-41, Academic, New York, 1968. (218) Zipkin, I., Piez, K. A., J. Dental Res. 1950, 29, 498.


RECEIVED October 27, 1969. Contribution Number 1118 from the Department of Nutrition and Food Science, Massachusetts Institute of Technology, Cambridge, Mass.


Dietary Chemicals vs. Dental Caries - ACS Publications

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