Dietary Chemicals vs. Dental Caries

8

Minerals: Calcium and Phosphorus

R O B E R T S. HARRIS

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Massachusetts Institute of Technology, Cambridge, Mass.

The results of over 130 studies with hamsters and rats indicate that phosphates exert a significant cariostatic action when added to caries-producing diets. Phosphates decrease in cariostatic activity depending on type of anion (cyclic-, trimeta-, tripoly-, hexameta-, ortho-, and pyro-, respectively) and type of cation (H, Na, K, Ca, and Mg, respectively). Organic phosphates (phytate, glycero-phosphate, etc.) are also effective. This cariostatic effect appears to result from a local action on the tooth as the phosphate passes through the mouth.

Since calcium and phosphorus are the dominant constituents of teeth, it is not surprising that dental investigators have long studied the effects of deficiency of these minerals upon the development of dental caries. The absorption of calcium from the intestine depends upon the amount of calcium ingested, the intestinal environment, and upon factors in food which may influence its uptake. H i g h intestinal p H , extremes in the C a / P ratios in the diet, and deficient supply of vitamin D may reduce calcium absorption. Foods rich i n oxalic acid (e.g., rhubarb and spinach) or i n phytates (e.g., unmilled cereals) may interfere with calcium absorption by forming insoluble compounds that are poorly absorbed. In spite of these factors, the human body has so great a capacity to adapt to variations in calcium intake that tooth formation is disturbed only when the deficiency is serious. The availability of calcium and phosphorus to the tissues depends upon the activity of the parathyroid glands. Abnormal parathyroid functioning may affect the development of unerupted teeth (31, 32). Sobel and Hanok (28) have demonstrated also that the composition of the tissue fluid surrounding the developing tooth is important, and that a relationship exists between the composition of the diet, the blood, and the teeth 116 Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

8.

Minerals:

HABRIS

Calcium

and

117

Phosphorus

w i t h respect to c a l c i u m , p h o s p h o r u s , a n d c a r b o n a t e content.

A deficiency

of c a l c i u m i n the tissue fluid m a y p r o v o k e a h y p o p l a s i a of the

enamel

w h i c h is s i m i l a r to that p r o d u c e d b y v i t a m i n D d e f i c i e n c y d u r i n g t o o t h development. A h y p o p l a s t i c l i n e t h r o u g h the w h o l e d e n t i t i o n has b e e n

described

as r e s u l t i n g f r o m a t e m p o r a r y d i s t u r b a n c e i n g r o w t h rate, y e t the d e n s i t y of the c a l c i u m i n this r e g i o n of the t o o t h is essentially the same as i n n o r m a l enamel.

V i t a m i n D h y p o p l a s i a i n c h i l d r e n does n o t

increase

caries s u s c e p t i b i l i t y , a n d a n osteomalacia r e s u l t i n g f r o m c a l c i u m - d e f i c i e n t diets does n o t l e a d to a n increase i n caries i n p r e g n a n t w o m e n or i n t h e i r Downloaded by UNIV LAVAL on July 12, 2016 | http://pubs.acs.org Publication Date: June 1, 1970 | doi: 10.1021/ba-1970-0094.ch008

offspring.

Dahlberg (5)

r e p o r t e d that neither c a l c i u m n o r v i t a m i n D

t a k e n d u r i n g p r e g n a n c y a n d l a c t a t i o n h a d a n influence i n caries d e v e l o p ment. T h e e v i d e n c e seems c o n c l u s i v e that alterations i n c a l c i u m n u t r i t i o n or i n c a l c i u m m e t a b o l i s m h a v e l i t t l e effect u p o n d e n t a l caries d e v e l o p m e n t i n h u m a n beings. T h e effects of deficiencies

a n d excesses of c a l c i u m a n d / o r

phos-

p h o r u s u p o n d e n t a l caries i n rats m a i n t a i n e d o n e x p e r i m e n t a l diets w e r e s h o w n c l e a r l y i n three experiments r e p o r t e d b y the H a l d i g r o u p ( 7 , 34).

It is g e n e r a l l y a g r e e d that a d i e t c o n t a i n i n g 0 . 5 %

33,

C a a n d 0 . 5 % P is

q u i t e a d e q u a t e f o r rat n u t r i t i o n . I n E x p e r i m e n t A ( T a b l e I ) , the P c o n tent of the d i e t w a s h e l d constant, a n d the C a content w a s adjusted to 0.5, 1.0, 2.0, a n d 3.0 times its r e q u i r e m e n t .

I n E x p e r i m e n t B , the C a content

was h e l d constant, a n d the P content was adjusted to 0.5, 1.0, 2.0, a n d 3.0 times its r e q u i r e m e n t .

F i n a l l y , i n E x p e r i m e n t C , the C a a n d P contents

w e r e adjusted c o n c u r r e n t l y to 0.5, 1.0, 2.0, or 3.0 times the r e q u i r e m e n t . Table I. Effects of Variations in C a and P Contents of Rat Diets upon Dental Caries Development

Exp.

Ca/P of % Ca in %Pin Diet Diet Diet

No. of Rats

Average No. of Lesions

Average Caries Score

Ref.

A

1:2.0 1:1.0 1:0.5 1:0.3

0.29 0.57 1.01 1.57

0.52 0.50 0.49 0.52

20 20 20 20

23 21 19 17

± =b ± =b

0.4 0.5 0.8 0.8

34 27 21 20

d= ± ± ±

1.5 1.3 1.2 1.2

B

1:0.5 1:1.0 1:2.0 1:3.0

0.49 0.50 0.50 0.50

0.24 0.52 0.98 1.48

40 40 40 40

22 18 13 11

=b zb ± ±

4.2 4.7 6.1 5.3

44 25 16 13

=b =b ± zb

18 11 8 8

(34)

C

1:1 1:1 1:1 1:1

0.25 0.50 1.00 1.50

0.25 0.50 1.00 1.50

15 15 15 15

24 21 18 17

=b =b ± db

2.4 1.4 3.5 4.0

47 33 21 20

± =b ± zb

15 11 6 4

(S3)

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

(7)

118

D I E T A R Y

C H E M I C A L S

VS.

D E N T A L

CARIES

D e f i c i e n t levels o f C a , P , o r b o t h , c a u s e d increases i n caries d e v e l o p ment.

T h e phosphorus-deficient diet was more cariogenic than the cal-

c i u m - d e f i c i e n t diet. Excesses o f either C a , P , o r b o t h c a u s e d decreases i n caries d e v e l o p m e n t . Excesses o f P w e r e m o r e cariostatic t h a n excesses of C a a n d the effects o n caries d e v e l o p m e n t w e r e greater w h e n t h e diets w e r e deficient o r excessive i n b o t h C a a n d P content.

I t is e v i d e n t that

the l e v e l o f d i e t a r y C a a n d P was i n f l u e n c i n g caries d e v e l o p m e n t i n rats u n d e r these s p e c i a l c o n d i t i o n s . Since p h o s p h o r u s is a m a j o r c o m p o n e n t o f t h e t o o t h , t h e d i e t m u s t s u p p l y l i b e r a l amounts, e s p e c i a l l y d u r i n g e a r l y g r o w t h a n d d e v e l o p m e n t .


A l t h o u g h t h e diets o f h u m a n beings n o r m a l l y c o n t a i n generous of p h o s p h o r u s , i t u s u a l l y is n o t u t i l i z e d efficiendy. p h o r u s i n foods f r o m p l a n t sources

amounts

M u c h of the phos-

(e.g., cereals, legumes, l e a f y vege-

t a b l e s ) is present as p o o r l y - s o l u b l e phytates w h i c h m u s t b e d e g r a d e d to orthophosphates b y e n z y m a t i c h y d r o l y s i s t o b e u t i l i z e d .

Furthermore,

e v e n w h e n p h o s p h o r u s is present as o r t h o p h o s p h a t e i t m a y react w i t h divalent minerals

(e.g., C a , M g , Z n ) i n t h e f o o d o r i n t h e i n t e s t i n a l

tract t o f o r m p o o r l y - s o l u b l e complexes.

T h i s explains w h y m o r e

than

5 0 % o f the p h o s p h o r u s i n g e s t e d i n the d i e t g e n e r a l l y is excreted w i t h o u t being absorbed. Investigators

have been

slow i n determining whether

phosphorus

p l a y s a r o l e i n d e n t a l caries d e v e l o p m e n t . P o s s i b l y this has b e e n because the C a / P ratio o f diets was b e i n g o v e r e m p h a s i z e d ( I I ) . L e n o x (18, 19, 20)

suggested that p h o s p h o r u s d e f i c i e n c y m i g h t b e the cause o f r a m p a n t

caries i n w h i t e p o p u l a t i o n s i n S o u t h A f r i c a w i t h o u t p r e s e n t i n g to s u p p o r t t h e concept.

evidence

This deduction resulted f r o m a n observation

that t h e excellent teeth i n n a t i v e b l a c k p o p u l a t i o n s r e s u l t e d f r o m c o n s u m i n g n a t u r a l u n r e f i n e d foods, w h i l e the p o o r teeth i n w h i t e p o p u l a t i o n s r e s u l t e d f r o m c o n s u m i n g r e f i n e d foods. I t has b e e n k n o w n for some t i m e that r e f i n e d foods lose c o n s i d e r a b l e m i n e r a l s , i n c l u d i n g phosphates, d u r i n g the m i l l i n g o f cereals a n d t h e r e f i n i n g o f sugar

(24).

P e r h a p s t h e earliest e x p e r i m e n t a l e v i d e n c e o f a c o r r e l a t i o n b e t w e e n l o w - p h o s p h o r u s diets a n d d e n t a l caries McCollum

was presented

by Klein and

( 1 5 ) , w h o later m i s t a k e n l y suggested that t h e p a r t i c l e size

of t h e c o r n i n t h e d i e t was responsible (16).

Klein and Shelling

(17),

A g n e w et al. (1), a n d R o s e b u r y a n d K a r s h a n (25) a l l o b s e r v e d a r e l a tionship between

l o w d i e t a r y P a n d h i g h d e n t a l caries

i n rats;

only

S h e l l i n g a n d A s h e r (26) f a i l e d to c o n f i r m this r e l a t i o n s h i p . H a r r i s et al. (13) a n d H a r r i s a n d N i z e l (10) later o b s e r v e d that the ash o f a m i x e d d i e t was cariostatic w h e n a d d e d to t h e d i e t o f hamsters. T h e y a n a l y z e d this a s h s p e c t r o g r a p h i c a l l y a n d c h e m i c a l l y , t h e n

com-

p o u n d e d a salt m i x t u r e w h i c h d u p l i c a t e d t h e m i n e r a l elements i n t h e f o o d ash, a n d d e m o n s t r a t e d that this salt m i x t u r e was s t r o n g l y cariostatic


8.

Minerals:

HARRIS

Calcium

also w h e n a d d e d to t h e diet.

and

Phosphorus

119

T h e y t h e n m o d i f i e d this salt m i x t u r e b y

o m i t t i n g o n e m i n e r a l element at a t i m e .

T h e cariostatic a c t i v i t y w a s

c o m p l e t e l y lost w h e n o n l y p h o s p h o r u s w a s o m i t t e d f r o m t h e salt m i x t u r e . T h u s , i t w a s d e m o n s t r a t e d that p o t a s s i u m o r t h o p h o s p h a t e is v e r y effective as a cariostatic agent, e v e n w h e n a d d e d to a d i e t a l r e a d y n u t r i t i o n a l l y a d e q u a t e i n p h o s p h o r u s content. D u r i n g t h e past d e c a d e , t h e results o f m o r e t h a n 150 studies h a v e b e e n p u b l i s h e d b y scores o f scientists w o r k i n g i n v a r i o u s parts o f t h e w o r l d w h o s u p p l e m e n t e d v a r i o u s c a r i e s - p r o d u c i n g diets b y different phosphate compounds. T h e y have been nearly unanimous i n reporting


that v a r i o u s types o f i n o r g a n i c a n d o r g a n i c phosphates are effective i n r e d u c i n g a n d e v e n p r e v e n t i n g d e n t a l caries i n rodents. N i z e l a n d H a r r i s (23) p u b l i s h e d a t h o r o u g h r e v i e w of this l i t e r a t u r e i n 1964. T h e l i t e r a t u r e i n d i c a t e d that ( a ) t h e anticaries activities of different types o f s o d i u m phosphates decrease i n t h e f o l l o w i n g o r d e r : t r i m e t a - , t r i p o l y - , h e x a m e t a - , o r t h o - a n d p y r o (14);

( b ) t h e salts o f t h e same a n i o n (e.g., o r t h o p h o s -

p h a t e ) d e c r e a s e d i n anticaries a c t i v i t y i n t h e f o l l o w i n g o r d e r : H > N a > K

>

Ca >

M g ; ( c ) o r g a n i c phosphates s u c h as N a g l y c e r o p h o s p h a t e ,

N a p h y t a t e , o r N a sucrose p h o s p h a t e are e q u a l l y as cariostatic as N a o r t h o p h o s p h a t e , a n d ( d ) s i m i l a r r e l a t i o n s h i p s w e r e f o u n d w h e n the v a r i ous phosphates w e r e c o m p a r e d i n rats, hamsters, o r c o t t o n rats. M c D o n a l d et al. (21) a d d e d 1 % N a H P 0 , 1 % N a H P 0 , o r 0 . 2 5 % 2

NaH P0 2

4

+

0.25% N a H P 0 2

4

4

2

4

to t h e c a r i o g e n i c diets o f rats to c o m p a r e

the cariostatic actions of a c i d , a l k a l i n e , a n d n e u t r a l f o r m s o f s o d i u m o r t h o p h o s p h a t e . T h e y r e p o r t e d caries r e d u c t i o n s of 61.4, 55.1, a n d 4 2 . 2 % , r e s p e c t i v e l y , after t h e diets h a d b e e n f e d f o r 150 days. T h u s , t h e a c i d p h o s p h a t e w a s t h e most active i n c o n t r o l l i n g caries a n d t h e n e u t r a l p h o s p h a t e m i x t u r e w a s the least effective. of others (14,23)

T h i s c o n f i r m e d the e v i d e n c e

that t h e a c i d i t y of phosphates does n o t interfere w i t h

t h e i r cariostatic a c t i o n . Present e v i d e n c e indicates that the anticaries effects o f phosphates are l o c a l , a c t i n g u p o n t h e surface layers o f t h e teeth (22).

A dramatic

cariostatic effect w a s n o t e d w h e n t h e p h o s p h a t e w a s f e d i m m e d i a t e l y after t o o t h e r u p t i o n . T h e m e c h a n i s m of t h e a c t i o n of p h o s p h o r u s is q u i t e different f r o m that of

fluorine.

N a v i a a n d H a r r i s (22)

n o t e d that

p h o s p h a t e delays t h e i n i t i a t i o n of caries, w h i l e fluorine retards the d e v e l o p m e n t o f caries after i t has been i n i t i a t e d . T h e cariostatic actions o f fluorine

a n d phosphates are s y n e r g i s t i c w h e n t h e y are f e d c o n c u r r e n t l y .

T h o u g h the e v i d e n c e is b y n o means c o n c l u s i v e , i t appears

that

p h o s p h a t e s u p p l e m e n t s m a y b e effective i n c o n t r o l l i n g d e n t a l caries i n h u m a n beings. II).

S i x c l i n i c a l studies h a v e b e e n c o n d u c t e d to date

Stralfors ( 2 9 ) , S t o o k e y et al.

(30),

a n d H a r r i s et al.

(8)

(Table added

phosphates to foods, f e d t h e m to c h i l d r e n d u r i n g p e r i o d s of 1 to 3 years,


120

DIETARY

C H E M I C A L S

Table II. Level Fed

%

Test Substance

Compound

P

Vehicle

No. of Subjects

D E N T A L

CARIES

Effects of Different

Age at Beginning Range

Average

Test Periot

Sugar & flour

163 114

6-15 6-15

-

2 2

0.36

Sugar, bread, & flour

1001 1101

8.5-9.5 8.5-9.5

9 9

2 2

0.0 2.0

0.36

Bread, cakes, & buns

350 390

7-14 7-14

10.2 10.2

3 3

CaHP0 • 2H,0

0.0 1.125 gm/ day

0.2 gm/ day

Chewing gum

129 138

6-18 6-18

12.4 12.4

2.5 2.5

NaH P0 °

0.0 1.0

0.24

Breakfast cereal

116 84

5-16 5-16

10.1 10.3

2 2

Ca sucrose phosphate

0.0 1.0

0.062

Flour, biscuits, syrup, & jam

632 408

5-17 5-17

CaHP0

0.0 2.0

0.456

CaHP0 • 2H 0

0.0 2.0

CaHP0 • 2H 0

4

4

2


%

VS.

4

2

4

2

4

-

1 1

N a H P 0 was replaced by mixture of NaH PO (0.74) and Na*HPO (0.26) at end of first year. a

2

4

2

4

4

a n d n o t e d " s i g n i f i c a n t " r e d u c t i o n s i n t h e d e v e l o p m e n t o f n e w caries, i n c o m p a r i s o n w i t h c o n t r o l g r o u p s o f c h i l d r e n f e d t h e same f o o d s w i t h o u t phosphate supplementation.

F i n n a n d Jamison

(6)

noted a reduction

i n caries d e v e l o p m e n t w h e n c h i l d r e n c h e w e d p h o s p h a t e - e n r i c h e d c h e w i n g g u m d a i l y d u r i n g 2 years, i n c o m p a r i s o n w i t h a c o n t r o l g r o u p that was given a n identical c h e w i n g g u m not fortified w i t h phosphate. O n the other h a n d , A v e r i l l a n d B i b b y ( 2 ) a n d S h i p a n d M i c k e l s e n ( 2 7 ) f a i l e d to observe significant caries effects i n s o m e w h a t s i m i l a r studies i n children. T h e a n i m a l a n d c l i n i c a l studies a r e n o t d i r e c t l y c o m p a r a b l e . I n most studies w i t h rodents, t h e p h o s p h a t e w a s i n c o r p o r a t e d i n t o t h e entire d i e t , a n d w a s c o n s u m e d c o n c u r r e n t l y w h e n e v e r a n y f o o d w a s eaten.

I n the

c l i n i c a l studies, t h e p h o s p h a t e w a s a d d e d t o o n l y a p o r t i o n o f t h e f o o d ( s u g a r a n d flour; sugar, b r e a d , a n d flour; b r e a d , cakes, a n d b u n s ; breakfast c e r e a l ; flour, b i s c u i t s , s y r u p , a n d j a m ; o r i n c h e w i n g g u m ) a n d n o t i n a l l foods. T h u s , t h e c h i l d r e n i n t h e c l i n i c a l studies r e c e i v e d less p h o s p h a t e , p o s s i b l y one-tenth as m u c h , p e r g r a m o f f o o d .


8.

Minerals:

HARRIS

Calcium

and

121

Phosphorus

Phosphates on Dental Caries in Children DMFT Increment per Child 5.6 5.0

DMFS

Incre% Reduc- ment tion over per Control Child 9.6 9.3

11

DFS

%

Reduction over Control

Increment per Child

%

Reduction over Control


4.64 4.43

4.5

8.12 7.41

9

-

3.12 2.54

19

5.9 4.7

20

5.60 4.50

36.3* 16.8

11.45 6.75

6

b

41.0 22.2

b

-

41 (m) 46(f)

50% & 40% reductions after 1 & 2 yrs., resp.

-

(29)

(27)

(6)

20

-

(SO)

b

6.56 5.47

e

Ref. (2)

3 0.27(m) 0.26(f) 0.16(m) 0.14(f)

4.49 2.86

Comments

Significant reduction in 5 to 12 yrs. age group/

16.6

(U)

Data from two observers. Results were essentially the same at end of two years (S). D i c a l c i u m p h o s p h a t e w a s u s e d i n f o u r o f t h e c l i n i c a l studies, s o d i u m

o r t h o p h o s p h a t e w a s u s e d i n t h e fifth, a n d c a l c i u m sucrose p h o s p h a t e w a s u s e d i n t h e s i x t h . H a r r i s et al. (8, 9,14)

a n d C a g n o n e et al. (4) d e m o n -

strated i n rats that s o d i u m t r i m e t a p h o s p h a t e is a p p r o x i m a t e l y five times as effective as a cariostatic agent as s o d i u m o r t h o p h o s p h a t e , a n d H a r r i s a n d N i z e l (12) h a v e s h o w n that p h o s p h o r u s i n t h e f o r m o f s o d i u m o r t h o p h o s p h a t e is p o s s i b l y three times m o r e effective t h a n p h o s p h o r u s i n c a l c i u m orthophosphate.

P h o s p h a t e i n c a l c i u m sucrose p h o s p h a t e is less

effective t h a n p h o s p h a t e i n s o d i u m o r t h o p h o s p h a t e . S o d i u m t r i m e t a p h o s p h a t e is t h e most effective o f a l l phosphates y e t tested i n a n i m a l s , is less t o x i c t h a n o r t h o p h o s p h a t e , a n d appears t o b e t h e c o m p o u n d o f c h o i c e f o r c l i n i c a l trials. C a l c i u m a n d p h o s p h o r u s c a n i n f l u e n c e t h e d e v e l o p m e n t o f caries w h e n a d d e d to t h e d i e t , t o c h e w i n g g u m , o r t o other carriers; p h o s p h a t e is m o r e effective t h a n c a l c i u m as a cariostatic agent, a n d b o t h c a l c i u m a n d p h o s p h a t e are effective e v e n w h e n a d d e d as s u p p l e m e n t s to diets already nutritionally adequate.


122

DIETARY CHEMICALS VS. D E N T A L CARIES


Literature

Cited

(1) Agnew, M . C., Agnew, R. S., Tisdall, F. F., J. Am. Dental Assoc. 1933, 20, 193. (2) Averill, H . M., Bibby, B. G., J. Dental Res. 1964, 43, 1150. (3) Beveridge, J., Gregory, G., Schamschule, R. G., Savage, D. C. L . , Med. J. Australia 1968, 2, 256. (4) Cagnone, L . D., Harris, R. S., Navia, J. M . , Proc. Intern. Assoc. Dental Res. 1968, Abst. 364, p. 128. (5) Dahlberg, B., Acta Genet. Statist. Med. (Basel) 1951, II, 57. (6) Finn, S. B., Jamison, H . C., J. Am. Dental Assoc. 1967, 74, 987. (7) Haldi, J., Wynn, W., Bentley, K. D., Law, M. L., J. Nutr. 1959, 67, 645. (8) Harris, R., Schamschula, R. G., Gregory, G., Roots, M . , Beveridge, J., Australian Dental J. 1967, 12, 105. (9) Harris, R. S., Das, S. K., Nizel, A. E., J. Dental Res. 1965, 44, 549. (10) Harris, R. S., Nizel, A. E., J. Dental Res. 1959, 38, 1142. (11) Ibid., 1964, 43, 1090. (12) Ibid., 1965, 44, 416. (13) Harris, R. S., Nizel, A. E., Gardner, D . S., Proc. Intern. Nutr. Congr., 4th, 1957, p. 195. (14) Harris, R. S., Nizel, A. E., Walsh, N. B., J. Dental Res. 1967, 46, 290. (15) Klein, H., McCollum, E . V., Science 1931, 74, 662. (16) Klein, H., McCollum, E . V., J. Dental Res. 1932, 13, 69. (17) Klein, H., Shelling, D . H., J. Dental Res. 1931, 11, 458. (18) Lennox, J., S. African Dental J. 1929, 3, 125. (19) Ibid., 1930, 4, 592. (20) Ibid., 1931, 5, 156. (21) McDonald, J. L . , Stookey, G. K., Muhler, J. C., Arch. Oral Biol. 1968, 13, 903. (22) Navia, J. M . , Lopez, H . , Harris, R. S., Arch. Oral Biol. 1968, 13, 779. (23) Nizel, A. E., Harris, R. S., J. Dental Res. 1964, 43, 1123. (24) Roos, A., "Kulturzerfall und Zahnverderbnis," Hans Huber, Bern, 1963. (25) Rosebury, T., Karshan, M., Arch. Pathol. 1935, 20, 697. (26) Shelling, D . H., Asher, D . E., J. Dental Res. 1933, 13, 363. (27) Ship, I. I., Mickelsen, O. J., J. Dental Res. 1964, 43, 1144. (28) Sobel, A. E., Hanok, A., J. Biol. Chem. 1948, 176, 1103. (29) Stralfors, A., J. Dental Res. 1964, 43, 1137. (30) Stookey, G. K., Carroll, R. A., Muhler, J. C., J. Am. Dental Assoc. 1967, 74, 752. (31) Widdowson, E . M . , Voeding, Neth. J. Nutr. 1962, 23, 62. (32) Wynn, W., J. Nutr. 1959, 67, 645. (33) Wynn, W., Haldi, J., Bentley, K. D., Law, M . L., J. Dental Res. 1960, 39, 1248. (34) Wynn, W., Haldi, J., Bentley, K. D., Law, M . L., J. Nutr. 1956, 58, 325. RECEIVED October 27,

1969.


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