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