4
Vitamins and Dental Caries
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SAMUEL DREIZEN University of Texas Dental Science Institute at Houston, Houston, Tex. 77025
Vitamins contribute to both the pathogenesis and preven tion of dental caries. During the formative period, vitamins A, C, and D are essential for proper deposition and calcification of tooth structure. Posteruptively, the vitamin-dental caries relationship is mediated primarily through the oral acidogenic microorganisms. The Β vitamins nicotinic acid, pantothenic acid, and biotin are necessary growth factors for most if not all of the oral acidogenic flora. Some strains also require an exogenous source of thiamine and riboflavin. As components of the coenzymes which participate in ana erobic glycolysis, thiamine and nicotinic acid promote acid production by microbial action on locally retained ingested carbohydrates. Unfortunately, none of the Β vitamins can be deleted safely from the diet for caries prevention without impairment of human health.
The
vitamins are a group of diverse organic compounds which are dietary in origin and indispensable for human health and well being. Most function as integral parts of enzyme systems involved in essential metabolic processes. As such, they are required in relatively small amounts in sharp contrast to the dietary macro-nutrients which contribute primarily to the structural makeup of cells and tissues. Dental caries is a posteruptive disease of the teeth resulting from the action of cariogenic oral microorganisms on susceptible tooth struc ture in the presence of a suitable substrate and a favorable local environ ment. Various vitamins have been associated with the pathogenesis and prevention of dental caries. Some are caries-conducive; others cariesdeterrent. Some affect the caries process by their presence; others by their absence. Some have a preemptive influence which is exerted on the size, shape, and structure of the teeth. Others operate posteruptively by influencing the quantity and composition of the saliva and the makeup 33 Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.
34 of
DIETARY
the
oral microbial
flora.
Evidence
C H E M I C A L S
of
the
D E N T A L
VS.
vitamin-dental
CARIES
caries
r e l a t i o n s h i p is d e t a i l e d i n this report. Vitamin
A
Effects of Deficiency. L a c k of v i t a m i n A w i l l p r o d u c e characteristic
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a b n o r m a l i t i e s i n the shape a n d structure of d e v e l o p i n g teeth, p r o v i d e d the d e f i c i e n c y is c h r o n i c e n o u g h a n d severe e n o u g h . mediated
through
alterations
i n the
T h e effects
highly specialized
are
odontogenic
e p i t h e l i u m l e a d i n g to disturbances i n histo- a n d m o r p h o d i f f e r e n t i a t i o n . I n the rat, avitaminosis A i n d u c e s e n a m e l h y p o p l a s i a , i r r e g u l a r a n d a t y p i c a l d e n t i n f o r m a t i o n , a n d e p i t h e l i a l i n v a s i o n of the d e n t a l p u l p
(79).
I n m a n the p r i m a r y h i s t o p a t h o l o g y is a m e t a p l a s i a of t h e e n a m e l - f o r m i n g cells a n d a n a t r o p h y of the e n a m e l o r g a n w h i c h is m a n i f e s t e d c l i n i c a l l y as e n a m e l h y p o p l a s i a (11, 23).
A v i t a m i n o s i s A is a rare cause of e n a m e l
h y p o p l a s i a i n the h u m a n , since deficiencies of the degree a n d d u r a t i o n r e q u i r e d to p r o d u c e d e t e c t a b l e d e n t a l defects are u s u a l l y not c o m p a t i b l e w i t h l i f e . B l o c h (10)
s t u d i e d 64 b l i n d D a n i s h c h i l d r e n w i t h gross e v i -
d e n c e of severe v i t a m i n A d e f i c i e n c y d u r i n g i n f a n c y a n d f o u n d neither c o n s p i c u o u s a b n o r m a l i t i e s i n the f o r m , p o s i t i o n , a n d consistency of the teeth n o r a n i n c r e a s e d p r e d i s p o s i t i o n to d e n t a l caries. (85)
Similarly, Shourie
f o u n d no greater i n c i d e n c e of d e n t a l caries i n I n d i a n c h i l d r e n w i t h
s k i n a n d eye lesions suggestive of v i t a m i n A d e f i c i e n c y t h a n i n a d e q u a t e l y nourished ethnically identical children. P a y n t e r a n d G r a i n g e r (71)
successfully m o d i f i e d the genetic
tem-
p l a t e of tooth m o r p h o l o g y b y r e s t r i c t i n g p r e g n a n t rats to a synthetic diet deficient i n v i t a m i n A d u r i n g the t i m e the m o l a r teeth w e r e b e i n g f o r m e d i n t h e o f f s p r i n g . T h e p r o c e d u r e caused the d e v e l o p m e n t of s m a l l m o l a r teeth i n the y o u n g to a degree w h i c h exceeded variation.
T h e size differences
the range of n o r m a l
w e r e not a c c o m p a n i e d b y gross
surface defects, severe h i s t o l o g i c changes,
tooth
m e t a b o l i c derangements,
or
a n increased caries s u s c e p t i b i l i t y . T h e o n l y e v i d e n c e of a d i r e c t r e l a t i o n s h i p b e t w e e n
dental
caries
a n d c h r o n i c v i t a m i n A d e f i c i e n c y is s u p p l i e d b y S a l l e y , B r y s o n , a n d E s h l e m a n (76),
w h o o b t a i n e d a significant increase i n caries i n hamsters
g i v e n a synthetic diet d e v o i d of v i t a m i n A . T h e c a r i e s - p r o m o t i n g p o t e n t i a l of v i t a m i n A d e f i c i e n c y w a s a s c r i b e d to a greatly r e d u c e d s a l i v a r y flow p r e c i p i t a t e d b y the d e f i c i e n c y r e l a t e d loss of secretory a c i n i i n the major a n d m i n o r s a l i v a r y glands. X e r o s t o m i a a t t r i b u t a b l e to a k e r a t i n i z i n g m e t a p l a s i a a n d i n f l a m m a t o r y reaction i n b o t h the s a l i v a r y g l a n d a c i n i a n d ducts has b e e n d e s c r i b e d i n h u m a n v i t a m i n A d e f i c i e n c y (4).
Un-
f o r t u n a t e l y , details of the c a r i o g e n i c i t y of the xerostomia i n these cases are l a c k i n g .
Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.
4.
D R E I Z E N
Vitamins
and
Dental
Caries
35
Effects of Excess. D i e t a r y s u p p l e m e n t s of v i t a m i n A neither s t i m ulate n o r suppress the caries t e n d e n c y i n c h i l d r e n (21, b y D a y a n d S e d w i c k (21)
64).
In a study
at least 6000 U . S . P . units of v i t a m i n A i n -
gested d a i l y i n tablet f o r m together w i t h a d d e d v i t a m i n D f o r 15 m o n t h s not o n l y f a i l e d to h a v e a b e n e f i c i a l effect o n the caries i n c i d e n c e , b u t a f f o r d e d n o m e a s u r a b l e p r o t e c t i o n to the n e w l y e r u p t e d teeth.
I n rats,
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a d d i t i o n of excessive amounts of w a t e r - s o l u b l e a n d f a t - s o l u b l e v i t a m i n s i n c l u d i n g v i t a m i n A d i d not alter s i g n i f i c a n t l y either the average n u m b e r or average extent of carious lesions i n a n i m a l s w h o s e t o o t h d e v e l o p m e n t was almost c o m p l e t e w h e n the s u p p l e m e n t s w e r e i n i t i a t e d Thiamine (Vitamin
(82).
Bj)
Effects of Deficiency. I n 1958 S h a r p e n a k (81) that a d e f i c i e n c y of cocarboxylase
r e v i v e d a n hypothesis
( t h i a m i n e p y r o p h o s p h a t e or d i p h o s -
p h o t h i a m i n e ) is a n i m p o r t a n t cause of d e n t a l caries because of a n acc u m u l a t i o n of p y r u v i c a c i d i n the d e n t a l a n d b o d y tissues.
This concept
lacks s u p p o r t i v e e v i d e n c e a n d is i n d i r e c t conflict w i t h studies b y R u s s e l l (75)
i n South Vietnam and Thailand and b y Afonsky (2)
China.
i n central
T h e y s h o w that c o n s u m p t i o n of a n u t r i t i o n a l l y i n a d e q u a t e t r a -
d i t i o n a l diet, l o w or deficient i n t h i a m i n e , is w h o l l y c o m p a t i b l e w i t h a l o w caries
prevalence.
Effects of Excess.
G o l l (34)
tested the s u p p o s i t i o n that t h i a m i n e
d e f i c i e n c y m a y be a n etiologic factor i n d e n t a l caries b y f e e d i n g cakes p r e p a r e d f r o m t h i a m i n e - r i c h ingredients to a s m a l l g r o u p of G e r m a n children.
T h e t h i a m i n e intake p e r c h i l d w a s thus increased b y 0.8 m g
per day.
N o r e d u c t i o n i n caries i n c i d e n c e was n o t e d i n the
p e r i o d of s u p p l e m e n t a t i o n .
A g a p o v a (3)
9-month
o b t a i n e d a decrease i n the
d e n t a l caries attack rate i n some of 75 c h i l d r e n g i v e n a d i e t a r y a d d i t i v e of 2 m g t h i a m i n e d a i l y f o r 2 years.
T h e decrease w a s a t t r i b u t e d to the
suppressive a c t i o n of t h i a m i n e o n the c a r i o g e n i c m i c r o o r g a n i s m s . m i n e has b e e n f o u n d to be bacteriostatic w h e n a d d e d to s a l i v a in
Thiavitro
at a l e v e l of 200 /xgrams per m l . , a c o n c e n t r a t i o n w h i c h far exceeds the 0.2 to 1.4 /ngrams p e r 100 m l . n o r m a l l y present i n h u m a n s a l i v a (8,
30).
I n contrast, w h e n present at a l e v e l of 2 /xgrams p e r m l . i n a c h e m i c a l l y d e f i n e d c o m p l e t e synthetic m e d i u m , t h i a m i n e is g r o w t h - p r o m o t i n g rather t h a n bacteriostatic f o r some strains of o r a l acidogens Riboflavin
(Vitamin
(25).
B) 2
Effects of Deficiency. A s s h o w n b y d e n t a l surveys i n the U n i t e d States ( 5 5 ) , G u a t e m a l a (46), N i g e r i a (91), S o u t h V i e t n a m a n d T h a i l a n d ( 7 5 ) , a d i e t deficient i n r i b o f l a v i n is not necessarily c o n d u c i v e to d e n t a l
Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.
36
DIETARY
C H E M I C A L S
VS.
D E N T A L
CARIES
d e c a y . Subjects w i t h s u b s t a n d a r d r i b o f l a v i n intakes a n d c l i n i c a l e v i d e n c e of t h e d e f i c i e n c y state w e r e f o u n d to h a v e a caries p r e v a l e n c e w h i c h was no higher a n d often m u c h lower than i n nutritionally superior cont r o l g r o u p s i n t h e same r e g i o n . A l t h o u g h r i b o f l a v i n is a n u t r i t i o n a l essent i a l f o r some strains of o r a l l a c t o b a c i l l i , most w i l l tolerate a r i b o f l a v i n - f r e e synthetic m e d i u m w h i c h is c o m p l e t e i n a l l other n u t r i t i o n a l
essentials
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(25,51). Effects of Excess. I n c l u s i o n of r i b o f l a v i n i n t h e d i e t o f rats i n amounts f a r i n excess of t h e i r n u t r i t i o n a l needs does n o t alter t h e i r s u s c e p t i b i l i t y to d e n t a l caries
(82).
T h e r e h a v e b e e n n o c o m p a r a b l e studies o n t h e
h u m a n level.
Nicotinic
Acid
(Niacin)
Effects of Deficiency. R e p o r t s f r o m v a r i o u s parts o f t h e w o r l d i n d i cate that e n d e m i c p e l l a g r i n s h a v e a l o w i n c i d e n c e o f d e n t a l caries 49, 74, 77).
(19,
T h e r e is c o n s i d e r a b l e e v i d e n c e that t h e l o w caries p r e v a l e n c e
a n d t h e n i c o t i n i c a c i d d e f i c i e n c y p r o d u c t i v e of p e l l a g r a are i n t e r r e l a t e d rather t h a n fortuitous.
N i c o t i n i c a c i d has p r o v e d to b e a n i r r e p l a c e a b l e
nutritional factor for the oral lactic a c i d - p r o d u c i n g bacteria N i c o t i n i c a c i d a m i d e acts as t h e f u n c t i o n a l g r o u p of
I a n d I I , e n z y m e s necessary f o r c o n v e r t i n g f e r m e n t a b l e to a c i d residues.
(25, 5 1 ) .
codehydrogenases carbohydrates
W i t h i n p h y s i o l o g i c l i m i t s , the a m o u n t of a c i d p r o d u c -
t i o n i n saliva—glucose m i x t u r e s , in vitro, is r e l a t e d d i r e c t l y t o t h e n i c o t i n i c a c i d content of t h e s a l i v a s a m p l e (24).
A d d i t i o n of antimetabolites of
n i c o t i n i c a c i d to s u c h m i x t u r e s c o m p l e t e l y i n h i b i t s a c i d f o r m a t i o n ( 2 5 , 53).
I n c o r p o r a t i o n of a m e t a b o l i c antagonist of n i c o t i n i c a c i d i n a n ex-
p e r i m e n t a l c a r i o g e n i c d i e t f e d w e a n l i n g rats f o r 150 days r e d u c e d t h e caries t e n d e n c y i n these a n i m a l s s i g n i f i c a n t l y (26).
Conversely, deletion
of n i c o t i n i c a c i d f r o m a n u t r i t i o n a l l y b a l a n c e d c a r i e s - p r o d u c i n g hamster d i e t r e s u l t e d i n a r e d u c t i o n i n caries i n c i d e n c e to a p p r o x i m a t e l y half that of t h e c o n t r o l g r o u p
(68).
Effects of Excess. K o s e r a n d K a s a i ( 5 2 ) f o u n d that c o m p a r a t i v e l y h u g e quantities of n i c o t i n i c a c i d of t h e o r d e r of 10,000 times t h e n u t r i t i o n a l r e q u i r e m e n t w i l l p r e v e n t c o m p l e t e l y t h e g r o w t h of n i c o t i n i c a c i d d e p e n d e n t b a c t e r i a in vitro.
E x p e r i m e n t a l l y , excessive amounts of n i c o -
t i n i c a c i d a n d other B v i t a m i n s increase t h e caries i n c i d e n c e i n hamsters (32)
a n d d o n o t influence caries s u s c e p t i b i l i t y i n rats (82).
Although
massive doses of n i c o t i n i c a c i d are b e i n g u s e d presently i n t r e a t i n g some cases o f h y p e r c h o l e s t e r e m i a i n m a n , there h a v e been n o reports of t h e effect of this t h e r a p y o n t h e h u m a n d e n t i t i o n .
Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.
4.
Vitamins
D R E I Z E N
Pyridoxine
(Vitamin
and
Dental
Caries
37
B) 6
Effects of Deficiency. T h e p o s s i b i l i t y of a r e l a t i o n s h i p b e t w e e n p y r i d o x i n e a n d d e n t a l caries w a s a d v a n c e d b y R i n e h a r t a n d G r e e n b e r g
(73)
w h o o b s e r v e d that m o n k e y s m a i n t a i n e d o n l o n g t e r m p y r i d o x i n e - d e f i c i e n t diets d e v e l o p extensive d e n t a l caries.
The pyridoxine deficiency-dental
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caries axis w a s a p p a r e n t o n l y after a m i n i m u m of 2 years of exposure to the deficient diets, w i t h l i t t l e or n o adverse d e n t a l effects n o t e d d u r i n g the first 24 s t u d y m o n t h s .
Strean a n d c o - w o r k e r s ( 9 0 )
restricted small
groups of hamsters to a c a r i o g e n i c d i e t w i t h a n d w i t h o u t a d d e d p y r i d o x i n e ( 5 0 m g / 1 0 0 grams d i e t ) f o r 10 m o n t h s a n d o b t a i n e d a significant r e d u c t i o n i n f r e q u e n c y a n d extent of caries i n the p y r i d o x i n e - s u p p l e m e n t e d g r o u p . L a t e r Strean et al. (89)
subjected hamsters to c a r i o g e n i c
diets l o w i n p y r i d o x i n e (0.5 p p m ) a n d h i g h i n p y r i d o x i n e (10
ppm)
f o r 7 m o n t h s a n d f o u n d a significant p y r i d o x i n e - a s s o c i a t e d d i m i n u t i o n i n caries f r e q u e n c y for the l o w e r teeth b u t not f o r the u p p e r teeth.
The
d i s t i n c t i o n i n the locale of caries p r o t e c t i o n w a s a s c r i b e d to differences i n the p y r i d o x i n e content of the s a l i v a i n various parts of the m o u t h , b u t n o c h e m i c a l e v i d e n c e w a s offered to s u p p o r t this c o n t e n t i o n . Effects of Excess. T h e caries p r e v e n t i v e p o t e n t i a l of p y r i d o x i n e has b e e n tested i n a n i m a l s a n d i n m a n w i t h e q u i v o c a l results. W y n n , H a l d i , a n d L a w (94)
i n c l u d e d r e l a t i v e l y large amounts of p y r i d o x i n e ( u p to 100
p p m ) i n a s y n t h e t i c h i g h sucrose d i e t o r i g i n a l l y a d e q u a t e i n p y r i d o x i n e content.
T h e a d d e d p y r i d o x i n e f a i l e d to r e d u c e the c a r i o g e n i c i t y of the
test d i e t w h e n f e d to rats of a caries-susceptible S t e i n m a n a n d H a r d i n g e (87)
strain.
In
contrast,
a t t a i n e d a n o t a b l e r e d u c t i o n i n caries i n -
c i d e n c e w h e n rats w e r e g i v e n a r a t i o n representative
of the t y p i c a l
A m e r i c a n d i e t s u p p l e m e n t e d w i t h p y r i d o x i n e to the extent of 16 m g per k g food. I n a s m a l l p i l o t s t u d y , Strean et al.
(89)
achieved a 40%
reduction
i n n e w carious lesions i n 14 c h i l d r e n , 10 to 15 years o l d , g i v e n lozenges c o n t a i n i n g 3 m g p y r i d o x i n e t h r i c e d a i l y f o r 1 year. T h e reference g r o u p w a s c o m p r i s e d of 14 c h i l d r e n g i v e n p l a c e b o lozenges. (18)
Cohen and Rubin
u s e d a n i d e n t i c a l testing p r o c e d u r e i n 120 test c h i l d r e n a n d
129
c o n t r o l c h i l d r e n , 11 to 14 years of age, for 1 year a n d r e p o r t e d a slight suppressive effect of the p y r i d o x i n e lozenges o n d e n t a l caries.
T h e dif-
ference b e t w e e n the caries attack rates i n the p y r i d o x i n e a n d p l a c e b o g r o u p s w a s not, h o w e v e r , statistically significant. I n adults the effects of p y r i d o x i n e s u p p l e m e n t s o n d e n t a l experience has b e e n tested a n d Schenone (45).
caries
i n pregnant w o m e n by H i l l m a n , C a b a u d ,
S t a r t i n g w i t h the 4 t h m o n t h of p r e g n a n c y , 198 r a n -
d o m l y selected p r e g n a n t w o m e n w e r e g i v e n 20 m g p y r i d o x i n e once d a i l y i n c a p s u l e f o r m , 169 w e r e g i v e n a total of 20 m g p y r i d o x i n e t h r i c e d a i l y
Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.
38
DIETARY
C H E M I C A L S
VS.
D E N T A L
CARIES
i n l o z e n g e f o r m , a n d 173 r e c e i v e d p l a c e b o p r e p a r a t i o n s a n d s e r v e d as controls.
E a c h regimen was f o l l o w e d u n t i l parturition. T h e group not
g i v e n a d d e d p y r i d o x i n e h a d a n average D M F increase of 1.42 c o m p a r e d w i t h 1.22 f o r t h e c a p s u l e g r o u p a n d 0.89 f o r t h e l o z e n g e g r o u p . T h e difference b e t w e e n t h e m e a n D M F i n c r e m e n t s of the c o n t r o l a n d c a p s u l e g r o u p s w a s n o t significant; that b e t w e e n t h e c o n t r o l a n d l o z e n g e g r o u p s
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w a s significant. S t r e a n ( 8 8 ) attributes t h e caries-deterrent a c t i o n of p y r i d o x i n e to a n a l t e r a t i o n of t h e o r a l flora f r o m a p r e d o m i n a n t l y h o m o f e r m e n t a t i v e l a c t i c a c i d - p r o d u c i n g t y p e to a p r e v a l e n c e o f h e t e r o f e r m e n t a t i v e f o r m s w h i c h p r o d u c e less l a c t i c a c i d a n d m o r e v o l a t i l e e n d p r o d u c t s .
Since
h o m o f e r m e n t a t i v e f o r m s d o n o t a n d h e t e r o f e r m e n t a t i v e forms d o u t i l i z e p y r i d o x i n e , t h e a d d i t i o n of p y r i d o x i n e creates a c o m p e t i t i v e system w h i c h eventuates i n s u p p r e s s i n g t h e h e a v y a c i d p r o d u c e r s . P a r t i a l s u p p o r t f o r this c o n t e n t i o n is s u p p l i e d b y P a l a z z o , C o b e , a n d P l o u m i s ( 7 0 ) , w h o showed
that
addition
of p y r i d o x i n e i n concentrations
ranging from
1:2000 to 1:200,000 to s u i t a b l e m e d i a i n h i b i t s h o m o f e r m e n t a t i v e strains of t h e o r a l flora a n d p r o m o t e s g r o w t h o f t h e h e t e r o f e r m e n t a t i v e
types.
A l t h o u g h p y r i d o x i n e has b e e n s h o w n to b e bacteriostatic against
some
strains o f o r a l m i c r o o r g a n i s m s w h e n a d d e d to s a l i v a i n a c o n c e n t r a t i o n of 20 m g p e r 100 m l ( 8 ) , levels of 200 m g p e r 100 m l f a i l e d t o affect a c i d p r o d u c t i o n i n i n c u b a t e d s a l i v a - g l u c o s e mixtures ( 2 8 ) .
A proper
e v a l u a t i o n of t h e role of p y r i d o x i n e i n t h e caries process awaits m o r e intensive microbiologic, chemical, a n d clinical investigation.
Other B Vitamins O t h e r B v i t a m i n s w i t h a p o t e n t i a l role i n t h e caries process are biotin, pantothenic acid, folic acid, a n d inositol. B i o t i n a n d pantothenic a c i d resemble n i c o t i n i c a c i d i n that t h e y are essential f o r the g r o w t h a n d a c i d p r o d u c t i o n of o r a l l a c t o b a c i l l i , s t r e p t o c o c c i , s t a p h y l o c o c c i , a n d yeasts i n p u r e a n d m i x e d c u l t u r e ( 2 5 , 51).
M a k i l a ( 5 4 ) f o u n d that the
m e a n f o l i c a c i d content of resting w h o l e s a l i v a i n e d e n t u l o u s d e n t u r e wearers a n d patients w i t h teeth l a r g e l y d e s t r o y e d b y caries is almost three times greater t h a n that i n subjects w i t h slight caries a c t i v i t y . It w a s c o n c l u d e d that either a h i g h s a l i v a f o l i c a c i d l e v e l promotes t h e d e v e l o p m e n t of caries, o r the c a r i e s - p r e c i p i t a t i n g factor leads to a n increase i n saliva folic a c i d concentration.
Significant caries r e d u c t i o n s h a v e
been
o b t a i n e d i n rats f e d c a r i o g e n i c sugar diets c o n t a i n i n g 0 . 0 1 - 0 . 1 % i n o s i t o l (67).
A d d i t i o n of 1.4% p h o s p h o r y l a t e d i n o s i t o l to a b r e a d - g l u c o s e r a t
d i e t decreased t h e i n c i d e n c e o f d e n t a l caries b y a n average o f 7 7 % a n d the caries severity score b y a n average of 9 1 % ( 5 9 ) . Studies b y M c C a n n ,
Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.
4.
D R E I Z E N
Vitamins
and
Dental
39
Caries
B r a d y , a n d G i l l e n ( 5 8 ) i n d i c a t e that e n a m e l m a y p i c k u p p h o s p h a t e f r o m p h o s p h o r y l a t e d i n o s i t o l b y i o n exchange a n d that the increase i n e n a m e l p h o s p h a t e contributes to the anticaries effectiveness of this c o m p o u n d i n rats.
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Vitamin C (Ascorbic
Acid)
Effects of Deficiency. E v i d e n c e that v i t a m i n C is essential f o r n o r m a l t o o t h d e v e l o p m e n t is d e r i v e d f r o m h i s t o l o g i c changes i n the c o n t i n u o u s l y f o r m i n g incisors of s c o r b u t i c g u i n e a pigs.
T h e s e range f r o m
d i s t u r b e d h i s t o d i f f e r e n t i a t i o n of the odontoblasts c u l m i n a t i n g i n a m o r p h o u s a n d i r r e g u l a r d e n t i n f o r m a t i o n to a cessation of d e n t i n d e p o s i t i o n a n d o v e r c a l c i f i c a t i o n of the p r e d e n t i n . A t r o p h i c changes i n the
enamel
e p i t h e l i u m m a y o c c u r i n the late stages g i v i n g rise to e n a m e l h y p o p l a s i a (13).
Boyle
(12)
studied deciduous and permanent
t o o t h germs
of
s c o r b u t i c infants a n d f o u n d n o a b n o r m a l i t i e s except f o r some s m a l l cysts a n d m i n u t e hemorrhages
i n a f e w specimens.
Teeth
from
scorbutic
adults s h o w p o r o t i c d e n t i n , p u l p a l h y p e r e m i a a n d e d e m a , a n d a l t e r e d secondary d e n t i n f o r m a t i o n
(93).
D e s p i t e the s t r u c t u r a l changes associated w i t h s c u r v y , W e s t i n w a s u n a b l e to demonstrate
any relationship between
(93)
v i t a m i n C defi-
c i e n c y a n d d e n t a l caries i n the g u i n e a p i g , m o n k e y , or m a n , n o r is there a n y significant c o r r e l a t i o n b e t w e e n
the v i t a m i n C content
of h u m a n
b l o o d , s a l i v a , or u r i n e a n d d e n t a l caries a c t i v i t y (15, 44, 8 0 ) .
Neverthe-
less, O t t (69)
m a i n t a i n s that d e n t a l caries c a n be e q u a t e d w i t h d i s t u r b e d
v i t a m i n C m e t a b o l i s m b u t offers little c l i n i c a l a n d no e x p e r i m e n t a l e v i dence to substantiate
this c l a i m .
H a n k e (39)
s u p p l e m e n t e d the
diets
of 323 c h i l d r e n w i t h a p i n t of orange juice a n d the juice of one l e m o n d a i l y a n d o b t a i n e d a n a u s p i c i o u s r e d u c t i o n i n the i n t e n s i t y of
caries.
A d m i n i s t r a t i o n of 90 m l . of orange juice d a i l y f a i l e d to sustain the r e d u c e d caries a c t i v i t y , c a s t i n g some d o u b t o n the specificity of a d e n t a l c a r i e s vitamin C deficiency relationship. Effects of Excess. V i t a m i n C has been s h o w n to be c a r i e s - p r o m o t i n g , caries-neutral, a n d c a r i e s - p r e v e n t i n g — t h e
specific role v a r y i n g w i t h the
p a r t i c u l a r investigator.
regards p h a r m a c o l o g i c a l l y ef-
T h u s , H a f e r (38)
fective doses of v i t a m i n C as c a r i o g e n i c since the a d m i n i s t r a t i o n of s u c h doses is f o l l o w e d i n a f e w weeks b y a rise i n l a c t o b a c i l l u s counts a n d b y a f a l l i n the n e u t r a l i z i n g p o w e r of the s a l i v a .
W h e n incorporated in
c a r i o g e n i c diets i n amounts r a n g i n g f r o m 0 . 5 - 2 . 5 % of the d a i l y r a t i o n , v i t a m i n C is w i t h o u t m e a s u r a b l e effect o n caries i n rats ( 5 0 ) sters ( 3 5 ) .
and in ham-
I n c h i l d r e n , G r a n d i s o n , Stott, a n d C r u i k s h a n k (36)
found
no significant m o d i f i c a t i o n i n the caries course of 20 c h i l d r e n g i v e n 200 m g v i t a m i n C d a i l y for 2 years.
D i e r k s (22)
r e p o r t e d that d a i l y doses
Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.
40
DIETARY
C H E M I C A L S
VS.
D E N T A L
CARIES
of 100 m g v i t a m i n C are p r o t e c t i v e against the s e c o n d a r y d e c a y w h i c h forms around
filling
m a r g i n s , as no s u c h lesions d e v e l o p e d i n c h i l d r e n
g i v e n v i t a m i n C f o r 1 year. T h e l a c k of a c o n t r o l g r o u p a n d the f a i l u r e to influence p r i m a r y caries l i m i t s the v a l u e a n d a p p l i c a b i l i t y of these findings.
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Vitamin
D
Effects of Deficiency. ficiency
T h e changes i n d u c e d b y a v i t a m i n D
de-
d u r i n g the f o r m a t i v e p e r i o d of the teeth v a r y w i t h the e x p e r i -
m e n t a l a n i m a l . I n a l l v i t a m i n D - d e p e n d e n t species, the first a n d most p r o m i n e n t d e f i c i e n c y c h a n g e is a l i n e of d i s t u r b e d c a l c i f i c a t i o n i n the dentin.
I n the severe cases this is f o l l o w e d b y a r e t a r d a t i o n of d e n t i n
f o r m a t i o n a n d a f a i l u r e of c a l c i f i c a t i o n of the p r e d e n t i n . I n the rat, e n a m e l f o r m a t i o n a n d c a l c i f i c a t i o n are unaffected b y a v i t a m i n D
deficiency,
b u t g u i n e a p i g s , dogs, a n d m a n m a y d e v e l o p h y p o p l a s t i c e n a m e l M e l l a n b y (61)
(40).
was the first to suggest that teeth w i t h i m p e r f e c t i o n s i n
the e n a m e l surface are m o r e susceptible to caries t h a n teeth w i t h o u t s u c h defects. refuted
(21,
T h i s concept has b e e n b o t h s u p p o r t e d (9, 20, 86),
w i t h M i i h l e m a n n (65)
expressing the
63)
and
contemporary
o p i n i o n that w h i l e s t r u c t u r a l irregularities a n d h y p o p l a s i a of the e n a m e l per
se d o not seem to increase caries s u s c e p t i b i l i t y , t h e y d o f a v o r post-
e r u p t i v e p l a q u e adherence a n d p o s s i b l y caries attack o w i n g to increased roughness. W h e t h e r r a c h i t i c c h i l d r e n have a greater t e n d e n c y to d e n t a l d e c a y t h a n n o n r a c h i t i c c h i l d r e n as has b e e n p r o c l a i m e d b y some (27, d i s p u t e d b y others M e l l a n b y (62)
(43,
84)
is s t i l l u n r e s o l v e d .
i m p l y that a n adequate
29)
and
N u m e r o u s studies
by
v i t a m i n D i n t a k e d u r i n g the
p e r i o d of tooth f o r m a t i o n i n c h i l d r e n is associated w i t h a r e d u c e d caries incidence.
A t t e m p t s to establish a r e l a t i o n s h i p b e t w e e n
dental
caries
a n d the v i t a m i n D content of the diet have been u n s u c c e s s f u l (95).
Di-
rect e v i d e n c e that h y p o p l a s i a is caused b y a d e f i c i e n c y of v i t a m i n D or that adequate v i t a m i n D per
se w i l l p r e v e n t h y p o p l a s i a or r e d u c e
i n c i d e n c e of d e n t a l caries is s t i l l l a c k i n g Effects of Excess.
the
(40).
T h e use of v i t a m i n D s u p p l e m e n t s to
control
d e n t a l caries is b e c l o u d e d b y a n inconsistency of results a n d i n t e r p r e t a tions.
C l a i m s for a caries-preventive
a c t i o n of v i t a m i n D range
from
u n m i t i g a t e d effectiveness regardless of age, diet, a n d f o r m a d m i n i s t e r e d (57)
to those t e m p e r e d b y s u c h l i m i t a t i o n s as: ( a ) v i t a m i n D p r o d u c e s
a substantial decrease i n the d e n t a l caries experience of c h i l d r e n w h e n g i v e n b e t w e e n 3 a n d 10 years of age b u t not w h e n g i v e n b e t w e e n a n d 16 years of age ( 5 ) ;
( b ) v i t a m i n D is m o r e b e n e f i c i a l against
w h e n a d d e d to a deficient diet t h a n to a w e l l b a l a n c e d d i e t (78);
Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.
11
caries (c)
4.
D R E I Z E N
Vitamins
and
Dental
Caries
41
v i t a m i n D decreases d e n t a l caries s u s c e p t i b i l i t y o n l y w h e n a d m i n i s t e r e d d u r i n g t h e f o r m a t i v e p e r i o d a n d not after a t o o t h has a l r e a d y e r u p t e d (6);
( d ) v i t a m i n D is m o r e effective against caries w h e n t a k e n as c o d
l i v e r o i l t h a n as i r r a d i a t e d ergosterol ( 5 6 ) .
Aebi (J)
reconciles studies
s h o w i n g a caries-deterrent a c t i o n of v i t a m i n D w i t h those w h i c h f a i l e d to c h a n g e the caries p a t t e r n (14,
21, 33, 48)
b y p o s t u l a t i n g that other
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factors i n the caries p i c t u r e m a y s u p p l e m e n t or negate the influence of v i t a m i n D . I n a m o r e p r o s a i c v e i n , S h a w (83)
ascribes the lack of effect
of v i t a m i n D to a l a c k of a n existing d e f i c i e n c y i n the subjects g i v e n the s u p p l e m e n t s . I n contrast, V o l k e r (92)
suggests that the s p e c i a l bene-
fits n o t e d w i t h c o d l i v e r o i l as c o m p a r e d w i t h other p r e p a r a t i o n s
of
v i t a m i n D c o u l d b e e x p l a i n e d b y the l o c a l a c t i o n of the fats c o n t a i n e d t h e r e i n rather t h a n b y the f o r m of the v i t a m i n D . Vitamin
E
V i t a m i n E is essential for m a i n t a i n i n g the e n a m e l o r g a n of the rat incisor.
A d e f i c i e n c y leads to p r e m a t u r e a t r o p h y a n d e d e m a of
the
p a p i l l a r y layer, d e p i g m e n t a t i o n , h y p o p l a s i a , b i z a r r e a n a t o m i c f o r m s , ret a r d e d e r u p t i o n rate, a n d cyst f o r m a t i o n i n the adjacent c o n n e c t i v e tissue (66,
72).
T h e p a r e n c h y m a of the s a l i v a r y glands is r e p l a c e d b y fat cells
a n d fibrous c o n n e c t i v e tissue (66).
Because of its a n t i o x i d a n t c a p a c i t y ,
v i t a m i n E has b e e n tested against s u l c u l caries i n the rat.
L e v e l s u p to
0 . 5 % a-tocopherol i n the d i e t f a i l e d to i n h i b i t either caries or the g r o w t h of selected c a r i o g e n i c m i c r o o r g a n i s m s Vitamin
(47).
K
O f a l l presently k n o w n v i t a m i n s , o n l y v i t a m i n K prevents a c i d form a t i o n w h e n a d d e d to s a l i v a - g l u c o s e mixtures in vitro
(28).
The anti-
b a c t e r i a l properties of n a t u r a l a n d synthetic v i t a m i n K stem f r o m t h e i r q u i n o n e structure w h i c h acts as a n e n z y m e p o i s o n a n d not f r o m the v i t a m i n a c t i v i t y (7, 17).
T h e efficacy of v i t a m i n K i n c o n t r o l l i n g d e n t a l
caries b y i n h i b i t i n g the enzymes i n v o l v e d i n the m i c r o b i a l d e g r a d a t i o n of c a r b o h y d r a t e s has b e e n s t u d i e d i n rats, hamsters, a n d m a n . I n rats, p r o l o n g e d a d m i n i s t r a t i o n of synthetic v i t a m i n K i n c o n c e n trations r a n g i n g f r o m 0.005 to 0.8%
of a c a r i o g e n i c d i e t f a i l e d to exert
a m e a s u r a b l e effect o n the caries i n c i d e n c e (41).
I n hamsters, v i t a m i n K
p r e v e n t e d d e n t a l d e c a y w h e n 1 m g was a d d e d to the d i e t every second d a y or w h e n 1 m g w a s injected i n t r a p e r i t o n e a l l y every t h i r d d a y
(31).
I n m a n , c h e w i n g a stick of g u m c o n t a i n i n g 0.75 m g 2 - m e t h y l - l , 4 - n a p h t h o q u i n o n e s o d i u m bisulfite a d d i t i o n c o m p o u n d ( s y n t h e t i c v i t a m i n K )
for
at least 10 m i n u t e s after each m e a l for a p e r i o d of 18 m o n t h s b y 58 sub-
Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.
42
DIETARY
C H E M I C A L S
VS.
D E N T A L
CARIES
jects r e d u c e d the d e v e l o p m e n t of n e w carious lesions b y f r o m 60 to 8 0 % d e p e n d i n g o n the basis o f c o m p a r i s o n (16).
T h e v a l i d i t y of these c o n -
clusions has b e e n c h a l l e n g e d b y S h a w (83)
w h o a n a l y z e d the d a t a i n
the absence of a statistical e v a l u a t i o n b y the authors a n d b y a subsequent s t u d y i n w h i c h c h e w i n g a s y n t h e t i c v i t a m i n K - c o n t a i n i n g g u m after i n g e s t i o n of f o o d o r d r i n k h a d no caries-suppressive
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and radiographic examination Vitamin
effect o n c l i n i c a l
(60).
P
Rutin, a compound w i t h vitamin P-like activity, and hesperidin, a n i n t e g r a l p a r t of the v i t a m i n P m o l e c u l e , e a c h w i t h a n t i o x i d a n t p r o p erties, h a v e b e e n i n v e s t i g a t e d f o r possible a n t i c a r i o g e n i c a c t i v i t y . N e i t h e r p r e v e n t e d caries i n rats w h e n i n c o r p o r a t e d i n a c a r i e s - i n d u c i n g d i e t n o r i n h i b i t e d the g r o w t h of selected b a c t e r i a u s u a l l y e n c o u n t e r e d i n the o r a l cavity.
I n a single t r i a l i n w h i c h rats w e r e f e d 0 . 5 %
h e s p e r i d i n , there
w a s a c t u a l l y a statistically significant increase i n caries score Vitamin
(47).
Mixtures
Effects of Deficiencies. G r e e n a n d H a r d e s (37) of short t e r m experiments
p e r f o r m e d a series
( 2 0 - 2 1 d a y s ) d e s i g n e d to test the effect of
m u l t i p l e v i t a m i n d e l e t i o n o n caries p r o d u c t i o n w i t h o u t i n d u c i n g f r a n k d e f i c i e n c y states. O m i s s i o n of a l l fat-soluble v i t a m i n s f r o m a c a r i o g e n i c d i e t w a s w i t h o u t effect o n the caries experience of w e a n l i n g a l b i n o rats, whereas a n absence of a l l w a t e r - s o l u b l e v i t a m i n s r e s u l t e d i n a significant decrease i n caries d e v e l o p m e n t .
T h e latter w a s a t t r i b u t e d , i n p a r t , to
a d i m i n i s h e d f o o d i n t a k e a n d d i s t u r b e d eating p a t t e r n since the rats f a i l e d to g r o w o n the w a t e r - s o l u b l e v i t a m i n deficient diet. Effects of Supplements. T h e a n t i c a r i o g e n i c effectiveness of m i x e d v i t a m i n preparations w a s i n v e s t i g a t e d i n a series of 436 h e a l t h y c h i l d r e n r a n g i n g i n age f r o m b i r t h to 5.5 years (42).
E a c h received a daily dietary
s u p p l e m e n t of 3000 to 4000 units v i t a m i n A , 400 units v i t a m i n D , 60 to 75 m g v i t a m i n C , 1.0 to 1.2 m g t h i a m i n e , 1.2 to 1.5 m g r i b o f l a v i n , a n d 8 to 15 m g n i a c i n a m i d e f o r 36 months. measurable fluoride
cariostatic
T h i s r e g i m e n f a i l e d to exert a
a c t i o n unless 0.5 to 1.0 m g
fluoride
as s o d i u m
w a s i n c o r p o r a t e d i n the d a i l y v i t a m i n s u p p l e m e n t .
Summary and
Conclusions
I n the p r e e m p t i v e p e r i o d , v i t a m i n s A , C , a n d D are essential f o r the p r o p e r d e p o s i t i o n a n d m i n e r a l i z a t i o n of t o o t h structure. A l t h o u g h w e l l f o r m e d teeth are not necessarily s y n o n y m o u s w i t h caries resistance,
Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.
4.
DREIZEN
Vitamins and Dental Caries
43
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such teeth may provide fewer opportunities for plaque attachment, plaque retention, and caries activity. In the posteruptive period, the vitamin-dental caries relationship is mediated primarily through the oral acidogenic flora. A l l cariogenic microorganisms are, to a certain extent, vitamin-dependent and require an exogenous supply of some or many of these nutrients. The spectrum of need varies with the particular organism. T h e Β vitamins nicotinic acid, pantothenic acid, and biotin are necessary growth factors for most, if not all, lactic acid bacteria. Some strains also require thiamine, ribo flavin, and folic acid. As components of the coenzymes involved i n anaerobic glycolysis, thiamine and nicotinic acid facilitate the production of organic acids by microbial action on retained ingested carbohydrates. Diets completely devoid of the vitamins which serve as essential growth factors for the oral acidogenic organisms or as glycolytic co enzyme components are caries-inhibitory. Unfortunately, these vitamins cannot be deleted safely from the diet without disastrous consequences to human health. Conversely, there is, as yet, no clear and uncontestable evidence that dietary supplements of any of the presently known vitamins is protective against human dental caries.
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4.
DREIZEN
Vitamins and Dental Caries
45
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