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The effect of dietary caffeine on urinary excretion of calcium, magnesium, sodium and potassium in healthy young females
NUTRITION RESEARCH, Vol. 4, pp. 43-50, 1984 0271-5317/84 $3.00 + .00 Printed in the USA. Copyright (c) 1984 Pergamon Press Ltd. All rights reserved.
THE
E F F E C T OF D I E T A R Y MAGNESIUM, SODIUM
C A F F E I N E ON U R I N A R Y E X C R E T I O N OF C A L C I U M , AND P O T A S S I U M IN H E A L T H Y Y O U N G F E M A L E S
L i n d a K. M a s s e y , PhD, and K e v i n J. W i s e , BS Food S c i e n c e and H u m a n N u t r i t i o n , W a s h i n g t o n S t a t e U n i v e r s i t y , P u l l m a n , WA 9 9 1 6 4 - 2 0 3 2
ABSTRACT Twelve female college students drank decaffeinated c o f f e e or tea to w h i c h O, 150 or 300 mg c a f f e i n e had been added. Each s u b j e c t had f a s t e d at l e a s t ten h o u r s b e f o r e d r i n k i n g e a c h of the t h r e e test b e v e r a g e s . U r i n e s a m p l e s w e r e c o l l e c t e d at one, two and three h o u r s after c a f f e i n e c o n s u m p t i o n . Total u r i n a r y t h r e e hour e x c r e t i o n of c a l c i u m , m a g n e s i u m and s o d i u m , but not p o t a s s i u m , i n c r e a s e d s i g n i f i c a n t l y after c a f f e i n e intake. The i n c r e a s e d o u t p u t of c a l c i u m and s o d i u m was m a i n l y due to s i g n i f i c a n t l y i n c r e a s e d u r i n a r y c a l c i u m and s o d i u m c o n c e n t r a t i o n s , w h i l e the i n c r e a s e d o u t p u t of m a g n e s i u m a p p e a r e d to be due to the c o m b i n a t i o n of both a slightly increased urinary magnesium c o n c e n t r a t i o n and v o l u m e . Total urine volume c o r r e l a t e d s i g n i f i c a n t l y w i t h d o s e of c a f f e i n e per b o d y w e i g h t when 300 mg of c a f f e i n e was c o n s u m e d . The e f f e c t s of c a f f e i n e on m i n e r a l e x c r e t i o n w e r e p r i m a r i l y due to c h a n g e s in m i n e r a l c o n c e n t r a t i o n and i n c r e a s e d u r i n a r y v o l u m e at one and two h o u r s .
KEY
WORDS:
Caffeine, potassium
urine,
calcium,
magnesium,
sodium,
INTRODUCTION D i e t a r y s u r v e y s have shown that the m a j o r i t y of the U.S. population consume caffeine-containing b e v e r a g e s daily, i n c l u d i n g all age g r o u p s (I,2). In a d d i t i o n to its well k n o w n s t i m u l a t o r y e f f e c t s on the c e n t r a l n e r v o u s s y s t e m , c a f f e i n e a f f e c t s a wide v a r i e t y of o t h e r t i s s u e s and o r g a n s , i n c l u d i n g the k i d n e y , w h e r e c a f f e i n e has a weak d i u r e t i c e f f e c t (1,3). The only p r e v i o u s study on the e f f e c t s of m e t h y l x a n t h i n e s on u r i n a r y m i n e r a l e x c r e t i o n found that in the s i n g l e s u b j e c t g i v e n an u n s p e c i f i e d i n j e c t e d dose of t h e o p h y l l i n e , u r i n a r y o u t p u t of c a l c i u m , m a g n e s i u m , s o d i u m and p o t a s s i u m i n c r e a s e d (4). Since o t h e r d i u r e t i c s are k n o w n to e f f e c t c a l c i u m and m a g n e s i u m e x c r e t i o n as w e l l as s o d i u m and p o t a s s i u m (5,6), it s e e m e d l o g i c a l to investigate caffeine. R e c e n t l y , H e a n e y and R e e k e r (7) r e p o r t e d that c a f f e i n e c o n s u m p t i o n c o r r e l a t e d w i t h a d e c r e a s e d c a l c i u m b a l a n c e in p r e m e n o p a u s a l f e m a l e s by i n c r e a s i n g both u r i n a r y and intestinal calcium losses. 43
44
MASSEY AND WISE: CAFFEINE AND URINARY MINERALS METHODS
T w e l v e h e a l t h y f e m a l e s , ages 2 2 - 3 0 y e a r s (mean 24.5 years) were r e c r u i t e d from s e n i o r and g r a d u a t e c l a s s e s at Washington State University. All s u b j e c t s w e r e w i t h i n 10% of i d e a l body w e i g h t and no s m o k e r s w e r e i n c l u d e d , s i n c e s m o k i n g i n c r e a s e s c a f f e i n e c l e a r a n c e (8). I n f o r m e d c o n s e n t was c o l l e c t e d a c c o r d i n g to h u m a n s u b j e c t r i g h t s p r o c e d u r e s of Washington State University. On t h r e e s e p a r a t e m o r n i n g s at one week i n t e r v a l s , each s u b j e c t d r a n k one of t h r e e b e v e r a g e s w h i c h r a n d o m l y c o n t a i n e d e i t h e r 150mg, 3 0 0 m g or no c a f f e i n e . The c a f f e i n e was w e i g h e d s e p a r a t e l y and a d d e d to a b e v e r a g e base w h i c h did not c o n t a i n caffeine. Ten s u b j e c t s chose d e c a f f e i n a t e d c o f f e e , one decaffeinated tea and one h e r b a l tea. Each s u b j e c t r e c e i v e d the same b e v e r a g e base all t h r e e e x p e r i m e n t a l days. Each s u b j e c t f a s t e d for at l e a s t ten h o u r s b e f o r e c o n s u m i n g the test b e v e r a g e , a l t h o u g h w a t e r was p e r m i t t e d ad l i b i t u m . Each s u b j e c t was asked not to c h a n g e e x e r c i s e or e a t i n g p a t t e r n s in the day b e f o r e each treatment. The e x p e r i m e n t was d e s i g n e d to r e s e m b l e the d i e t a r y p a t t e r n of b r e a k f a s t s k i p p i n g , w i t h the s u b s t i t u t i o n of a caffeine-containing b e v e r a g e for the m o r n i n g m e a l . The e x p e r i m e n t a l p r o c e d u r e was m o d e l e d a f t e r that of A l l e n et al. (9). Each s u b j e c t e m p t i e d her b l a d d e r , then d r a n k 240 ml of the test b e v e r a g e c o n t a i n i n g a b l i n d e d , r a n d o m - o r d e r e d , a m o u n t of c a f f e i n e or no c a f f e i n e . At one, two and t h r e e hours, e a c h s u b j e c t e m p t i e d her b l a d d e r , c o l l e c t i n g all u r i n e p r o d u c e d . U r i n e p r o d u c t i o n at all time p o i n t s was e n h a n c e d by h a v i n g each s u b j e c t d r i n k an a d d i t i o n a l 240 ml of d i s t i l l e d w a t e r at h o u r s one and two. The s u b j e c t s were o n l y a l l o w e d m i n i m a l p h y s i c a l m o v e m e n t and m o s t of the s u b j e c t s read or s l e p t d u r i n g the three-hour experimental period. U r i n e v o l u m e s w e r e m e a s u r e d , then c o n c e n t r a t e d HC1 (5% v o l : v o l ) was a d d e d . U r i n e s a m p l e s were f r o z e n u n t i l analy'zed. All g l a s s w a r e used for c o l l e c t i n g , m e a s u r i n g , s t o r i n g or a n a l y z i n g s a m p l e s was a c i d - w a s h e d and r i n s e d in d e i o n i z e d distilled water. C a l c i u m and m a g n e s i u m w e r e d e t e r m i n e d u s i n g a t o m i c a b s o r p t i o n s p e c t r o s c o p y on a l i q u o t s d i l u t e d in l a n t h i u m o x i d e c a r r i e r s , w h i l e s o d i u m and p o t a s s i u m were d e t e r m i n e d u s i n g f l a m e p h o t o m e t r y of u n d i l u t e d a l i q u o t s . S a m p l e s of HCI and w a t e r s used for the e x p e r i m e n t were a n a l y z e d and d e t e r m i n e d not to have d e t e c t a b l e a m o u n t s of t h e s e m i n e r a l s . H a b i t u a l c a f f e i n e c o n s u m p t i o n of each s u b j e c t from all b e v e r a g e s and m e d i c a t i o n s was d e t e r m i n e d by q u e s t i o n n a i r e . C a f f e i n e c o n t e n t of b e v e r a g e s and m e d i c a t i o n s was c a l c u l a t e d f r o m the v a l u e s of P e n n i n g t o n and C h u r c h (10). C o n s u m p t i o n of c h o c o l a t e and o t h e r c o c o a p r o d u c t s was not d e t e r m i n e d s i n c e the predominant methylxanthine in c o c o a p r o d u c t s is t h e o b r o m i n e (11), w h i c h has very l i t t l e d i u r e t i c or s t i m u l e n t e f f e c t (12). One way a n a l y s i s of v a r i a n c e was used to a n a l y z e the e f f e c t of c a f f e i n e c o n s u m p t i o n on t o t a l and h o u r l y u r i n e v o l u m e s , u r i n e ion c o n c e n t r a t i o n s and ion e x c r e t i o n . Linear regression was used to a n a l y z e the r e l a t i o n s h i p b e t w e e n c a f f e i n e dose per
MASSEY AND WISE: CAFFEINE AND URINARY MINERALS body weight and water and ion e x c r e t i o n . between low users and moderate users were t-test.
45
Potential d i f f e r e n c e s d e t e r m i n e d using a
RESULTS Caffeine c o n s u m p t i o n had only a weak, n o n - s i g n i f i c a n t , d i u r e t i c effect (Table i), However urinary c o n c e n t r a t i o n s of sodium and calcium almost doubled after the higher caffeine dose (Table i). Urinary m a g n e s i u m and p o t a s s i u m c o n c e n t r a t i o n did not change s i g n i f i c a n t l y .
TABLE 3 Hour
Urine
Volume
(ml)
CALCIUM
(mg/l)
MAGNESIUM SODIUM
(mg/l)
(mg/l)
POTASSIUM ~ean
(mg/l)
• standard
and Mean
Mineral
Caffeine dose 150
0 URINE
i. Concentration
(mg) 300
F
p
463•
525•
626•
1.49
N.S.
43.8•
54.2•
74.2•
3.9
25.1•
30.0•
28.9•
1.09
N.B.
103•
175•
198•
5.59
<.025
112•
139•
108•
0.40
N.S.
<
.05
deviation
Total urinary e x c r e t i o n of calcium and sodium more than doubled due to the combined effect of increased c o n c e n t r a t i o n and volume (Table 2). Total m a g n e s i u m e x c r e t i o n increased 50% due to the combined effect of increased c o n c e n t r a t i o n and volume. The increased p o t a s s i u m e x c r e t i o n was entirely due to i n c r e a s e d urine volume and was not s i g n i f i c a n t l y d i f f e r e n t after caffeine consumption.
TABLE 3 Hour
0 CALCIUM
(mg)
MAGNESIUM SODIUM
(mg)
POTASSIUM ~Mean
(mg)
(mg)
Total
2.
Mineral
Caffeine dose 150
Excretion * F
(mg)
p
30O
18.7•
27.2•
45.3•
7.41
< .005
i0.3~4.1
11.7•
15.2•
3.52
<.05
467•
812•
1133•
9.77
<.oo5
454•
490•
599•
1.90
N.S.
• standard
deviation
46
MASSEY AND WISE: CAFFEINE AND URINARY MINERALS
T o t a l u r i n e v o l u m e for each s u b j e c t c o r r e l a t e d significantly with the dose of c a f f e i n e c o n s u m e d per kg b o d y w e i g h t at the h i g h e s t dose of c a f f e i n e (r= - 0 . 7 3 , p < . 0 5 ) . H o w e v e r , t h e r e was no c o n s i s t e n t d o s e - d e p e n d e n t e f f e c t on t o t a l e x c r e t i o n of any ion. U r i n e v o l u m e did not d i f f e r s i g n i f i c a n t l y over the t h r e e hour e x p e r i m e n t a l o b s e r v a t i o n at any c a f f e i n e dose, nor did u r i n e v o l u m e d i f f e r s i g n i f i c a n t l y with caffeine dose at any of the h o u r l y c o l l e c t i o n s ( F i g u r e 1). C a f f e i n e had its g r e a t e s t e f f e c t on c a l c i u m c o n c e n t r a t i o n at one hour a f t e r its c o n s u m p t i o n ( F i g u r e i), and at both one and two h o u r s c a l c i u m c o n c e n t r a t i o n s were significantly (p < . 0 5 ) r e l a t e d to c a f f e i n e d o s e . A f t e r the c o n s u m p t i o n of 300 mg caffeine, calcium concentrations declined significantly (p < . 0 2 5 ) b e t w e e n one and t h r e e h o u r s . At the th i r d h o u r , c a l c i u m concentrations were not s i g n i f i c a n t l y d i f f e r e n t i r r e g a r d l e s s of caffeine dose. T o t a l c a l c i u m e x c r e t i o n at each h o u r l y s a m p l e p o i n t was s i g n i f i c a n t l y r e l a t e d to the c a f f e i n e dose (p < . 0 2 5 ) . Sodium concentration and t o t a l s o d i u m o u t p u t c l o s e l y p a r a l l e l e d that of c a l c i u m , and b o t h d i f f e r e d s i g n i f i c a n t l y (p < . 0 2 5 ) w i t h c a f f e i n e dose at h o u r s one and two. M a g n e s i u m and p o t a s s i u m concentrations did not c h a n g e s i g n i f i c a n t l y due to c a f f e i n e consumption, although decreased concentrations w e r e seen at h o u r s one and two at all c a f f e i n e loads, p o s s i b l y due to a water-induced diuresis. Five of the s u b j e c t s h a b i t u a l l y c o n s u m e d l o w a m o u n t s of c a f f e i n e , only 13-85 mg d a i l y , w h i l e seven s u b j e c t s h a b i t u a l l y c o n s u m e d a v e r a g e a m o u n t s , b e t w e e n 230 and 435 mg d a i l y . When d a t a was a n a l y z e d for t h e s e two s u b g r o u p s , the m o d e r a t e c a f f e i n e u s e r s did not s h o w c o n s i s t e n t l y l o w e r i n c r e a s e s in total ion excretion, s u g g e s t i n g that they had not d e v e l o p e d t o l e r a n c e to the r e n a l e f f e c t s of c a f f e i n e . Further study with larger populations and a g r e a t e r r a n g e of i n t a k e s is n e e d e d b e f o r e the p o s s i b i l i t y of t o l e r a n c e can be r u l e d out.
DISCUSSION In this small s a m p l e of y o u n g h e a l t h y w o m e n , c a f f e i n e consumption i n c r e a s e d u r i n a r y l o s s e s of c a l c i u m , m a g n e s i u m and sodium. The a m o u n t of c a f f e i n e n e e d e d to s h o w t h e s e e f f e c t s was not l a r g e , i n d e e d the h i g h e s t dose used, 300 mg, was the a v e r a g e a m o u n t c o n s u m e d d a i l y by t h e s e s u b j e c t s . In the r e c e n t USDA food consumption s u r v e y (2), d i e t a r y i n t a k e s of c a l c i u m and m a g n e s i u m did not m e e t the R e c o m m e n d e d D i e t a r y A l l o w a n c e s for y o u n g w o m e n . T h e r e is i n c r e a s i n g c o n c e r n that l i f e l o n g s u b o p t i m a l c a l c i u m s t a t u s may p r e d i s p o s e a d u l t s to the d e v e l o p m e n t of o s t e o p o r o s i s in l a t e r y e a r s (13, 14). Similarly marginal magnesium status has been s u g g e s t e d to be a c o n t r i b u t i n g f a c t o r for both bone loss and c a r d i o v a s c u l a r d i s e a s e (15). H e a n e y and R e c k e r (7) r e p o r t e d that c o n s u m p t i o n of c a f f e i n e - c o n t a i n i n g beverages varied i n v e r s e l y w i t h the c o n s u m p t i o n of d a i r y p r o d u c t s , w h i c h are e x c e l l e n t s o u r c e s of d i e t a r y c a l c i u m and m a g n e s i u m . Thus, a d i e t a r y p a t t e r n of h i g h c a f f e i n e c o n s u m p t i o n in c o m b i n a t i o n w i t h a low c a l c i u m and m a g n e s i u m i n t a k e may s t r e s s the h o m e o s t a t i c mechanisms maintaining c a l c i u m and m a g n e s i u m s t o r e s .
MASSEY AND WISE: CAFFEINE AND URINARYMINERALS
47
20"
~%~
OMG | 150MG A 300 MG
~
T I & "~
15,
Z L,u
~
10~
s
m Z
s
10"
8 |
-~.~,
250-
200-
150.
100" !
2 HOURS
FIG.1 Mean hourly calcium excretion, urine calcium concentraitons and urine volumes of twelve healthy young adult females after consuming both doses of caffeine, and the control decaffeinated beverage.
48
MASSEY AND WISE: CAFFEINE AND URINARY MINERALS
If the c a f f e i n e s o u r c e in the d i e t is c o f f e e , m a g n e s i u m l o s s e s due to c a f f e i n e may be small c o m p a r e d to the m a g n e s i u m c o n t e n t of the c o f f e e c o n s u m e d , w h i c h is 16 mg per 8 oz. cup (10). A c c o r d i n g to the USDA survey data, a d u l t s 23 years and o l d e r d e r i v e d 12 to 21% of their d i e t a r y m a g n e s i u m from the n o n a l c o h o l i c b e v e r a g e group, m a i n l y from c o f f e e (2). However, a l t h o u g h c o f f e e is a good s o u r c e of d i e t a r y m a g n e s i u m , it only c o n t a i n s 5 mg c a l c i u m per 8 oz. cup (10). I n c r e a s e s in u r i n a r y c a l c i u m and m a g n e s i u m do not n e c e s s a r i l y c a u s e d e p l e t i o n of body t i s s u e s t o r e s of these minerals. I n c r e a s i n g s o d i u m c o n s u m p t i o n from 75 to 240 meq d a i l y i n c r e a s e d u r i n a r y c a l c i u m o u t p u t from 110 to 167 mg, but i n t e s t i n a l a b s o r p t i o n i n c r e a s e d from 39% to 49%, w h i c h c o m p e n s a t e d for the i n c r e a s e d u r i n a r y c a l c i u m e x c r e t i o n (18). H o w e v e r , H e a n e y and R e c k e r (7) found that i n c r e a s e d c a f f e i n e c o n s u m p t i o n c o r r e l a t e d w i t h i n c r e a s e d fecal c a l c i u m loss as well. Several other dietary components, including protein (5,7,17), a l c o h o l (5) and g l u c o s e (5,18) i n c r e a s e u r i n a r y c a l c i u m e x c r e t i o n , as well as c a f f e i n e and s o d i u m , so some i n d i v i d u a l s may not be able to c o m p e n s a t e for the a d d i t i o n a l u r i n a r y l o s s e s c a u s e d by c a f f e i n e . I n c r e a s e s in u r i n a r y m i n e r a l e x c r e t i o n w e r e g r e a t e s t at one hour, then fell in the f o l l o w i n g two hours. A f t e r oral c o n s u m p t i o n of 300 mg c a f f e i n e , s e r u m c o n c e n t r a t i o n s peak one hour later, but d e c l i n e s l o w l y since c a f f e i n e has an a v e r a g e h a l f - l i f e of three to four hours (19). T h e r e f o r e , the r e l a t i v e l y r a p i d r e t u r n to usual m i n e r a l c o n c e n t r a t i o n s and t o t a l e x c r e t i o n are not l i k e l y to be due to d e c r e a s e s in c a f f e i n e c o n c e n t r a t i o n s . S t u d i e s c o m p a r i n g the r e s p o n s e of n o r m a l and h y p o p a r a t h y r o i d men to c a l c i t o n i n i n f u s i o n s u g g e s t that these s e c o n d a r y d e c r e a s e s could be m e d i a t e d by p a r a t h y r o i d h o r m o n e (20). P a r a t h y r o i d h o r m o n e , w h i c h in h u m a n s d e c r e a s e s net c a l c i u m e x c r e t i o n , a p p e a r s to act by e l e v a t i n g cAMP l e v e l s in the tubule (21). High d o s e s of m e t h y l x a n t h i n e s , i n c l u d i n g c a f f e i n e , e l e v a t e i n t r a c e l l u l a r cAMP l e v e l s by i n h i b i t i n g p h o s p h o d i e s t e r a s e . H o w e v e r , rats g i v e n 8.69 m g / k g c a f f e i n e for four weeks, a h i g h e r dose than our s u b j e c t s r e c e i v e d , had no s i g n i f i c a n t c h a n g e s in e i t h e r p l a s m a or u r i n a r y c A M P l e v e l s (22). The s t u d y by Agus et al (21) also s u g g e s t s that the u r i n a r y e f f e c t s o b s e r v e d in this study are p r o b a b l y not m e d i a t e d by cAMP. They fed d i b u t y r y l c y c l i c a d e n o s i n e m o n o p h o s p h a t e dogs, and found d i b u t y r y l cAMP d e c r e a s e d total u r i n a r y c a l c i u m , even t h o u g h c a l c i u m and s o d i u m r e s o r p t i o n was i n h i b i t e d in the p r o x i m a l tubule. Thus the e f f e c t s of c a f f e i n e o b s e r v e d in this s t u d y are not c o n s i s t e n t w i t h the e f f e c t of c a f f e i n e a c t i n g s o l e l y to i n h i b i t p h o s p h o d i e s t e r a s e , thus e l e v a t i n g i n t r a c e l l u l a r c A M P l e v e l s in the r e n a l t u b u l e . I n s u l i n , like c a f f e i n e , i n c r e a s e s net c a l c i u m e x c r e t i o n . H o w e v e r , i n s u l i n d e c r e a s e s , not i n c r e a s e s , s o d i u m e x c r e t i o n (8). Both W a c h m a n et al (23) and R a p t i s et al (24) r e p o r t e d that n e i t h e r blood g l u c o s e nor s e r u m i n s u l i n was e l e v a t e d f o l l o w i n g c a f f e i n e c o n s u m p t i o n , so it seems u n l i k e l y that the i n c r e a s e d u r i n a r y s e c r e t i o n of m i n e r a l s is s e c o n d a r y to an i n s u l i n elevation. I n t e r e s t i n g l y , c a f f e i n e ' s e f f e c t s are s i m i l a r to t h o s e of s a l m o n c a l c i t o n i n in man (20). C a f f e i n e c o n s u m p t i o n i n c r e a s e s u r i n a r y c a t e c h o l a m i n e o u t p u t (25, 26), so c a f f e i n e ' s
MASSEY AND WISE: CAFFEINE AND URINARY MINERALS
49
renal effects could be mediated by the s y m p a t h e t i c nervou~ system. Another u n e x p l o r e d p o s s i b i l i t y is that p r a s t a g l a n d i n s may be the p h y s i o l o g i c a l agents. Further work is needed to d e t e r m i n e the m e c h a n i s m s actually involved.
ACKNOWLEDGMENTS This research Project 0457,
was supported by the A g r i c u l t u r a l Re~ear~h Center, Wash. State Univ. S c i e n t i f i c paper NQ~ 6558.
REFERENCES 1. and
GRAHAM, DM. Caffeine-its b i o l o g i c a l effects. Nutr.
identity, dietary sourges, Rev. 36:97-102, 1978.
intake
2. Science and Education A d m i n i s t r a t i o n . Food and N~tri~nt Intakes of I n d i v i d u a l s in i day i__nnth__~e United States, ~ i ! ~ , 1977. W a s h i n g t o n , D.C.:U.S. D e p a r t m e n t of A g r i c u l t u r e ~ 1980. 3. STEPHENSON, caffeine on man.
P.E. P h y s i o l o g i c and p s y c h o t r o p i c effect~ J. Am. Diet. Assoc. 71:240-247, 1977.
4. BLUMGART, H.L., GILLIGAN, D.R., LEVY, VOLK, M.C. Action of diuretic drugs. I. normal persons. Arch. Int. Med. 54:40-81,
R.C., BROWN, M~G,, Action of d i u r e t i c s 1934.
5. LEMANN, J., ADAMS, N.D., GRAY, R.W. Urinary c a l c i u ~ excretion in human beings. New Eng. ~. Med. ~ 0 1 : 5 3 5 - 5 4 1 , 6. YU, T., BERGER, L., SARKOZI, L., KAUNG, C. d i u r e t i c s on urate and calcium e x c r e t i o n . Arch. 141:915-919, 1981. 7. HEANEY, R.P., RECKER, R.R. and caffeine on calcium balance 99:46-55, 1982.
of
Effeeta Intern.
in
1979. Qf ~ed
Effects of n i t r o g @ n , p h o s p h o r u s , in women. ~. Lab. Cili~ ~ ~ ,
8. PARSONS, W.D., NELMS, A.H. Effect of smoking clearance. Clin. Pharmacol. Ther. 24:40-45, 1978,
Q n caffeine
9. ALLEN, L.H.,BLOCK, G.D., WOOD, R.J., BR~CE, G,F. The rele of insulin and p a r a t h y r o i d hormone in the p r o t e i n , i ~ d u Q e d calciuria of man. Nutr. Res. 1:3-11, 1981. 10. PENNINGTON, J.A.T., commonly used. 13th ed.
CHURCH, H.N. New York, NY:
Food values of p ~ t ~ o n s HarPer & ROW. !9~0,
11. ZOUMAS, B.L., KREISER, W.R., MARTIN, R.A. T h e o b r o m i ~ e and caffeine content of c h o c o l a t e products. ~. F o o d Sci. 4 5 : 3 1 ~ - 3 1 6 , 1980. 12. DORFMAN, L.J., JARVIK, M.E. C o m p a r a t i v e s t i m u l a n t and diuretic actions of caffeine and t h e o b r o m i n e in man. Clin. Pharmacol. Ther. 11:869-872, 1970.
50
MASSEY AND WISE: CAFFEINE AND URINARY MINERALS
13. AVIOLI, L.V. Postmenopausal osteoporosis: cure. Fed. Proc. 40:2418-2422, 1981. 14. SEEMAN, the elderly.
prevention
E., RIGGS, B.L. Dietary prevention Geriatrics 36:71-79, 1981.
of bone
vers~s
loss
15. SEELIG, M.S. M_~agnesium deficienc F in the p a t h o g e n e ~ i s disease. New York, NY:Plenum. 1980.
in
o__f
16. BRESLAU, N.A., MCGUIRE, J.L., ZERWEKH, J.E., PAK, C.Y.C. The role of dietary sodium on renal excretion and intestinal absorption of calcium and on vitamin D metabolism. 2" C~in. Endocrin. Metab. 55:369-373, 1982. 17. ALTCHULER, S.I. Nutr. Res. 2:193-200,
Dietary 1982.
protein
and
calcium
loss;
a review,
18. ULMANN, A., AUBERT, J., BOURDEAU, A., CHEYNEL, C., BADER, C, Effects of weight and glucose ingestion on urinary calcium and phosphate excretion: implications for calcium lithiasis. ~, Clin. Endocrin. Metab. 54:1063-I068, 1982. 19. NEWTON, R., BROUGHTON, L.J., LIND, M.J., MORRISON, P.J., ROGERS, H.J., BRADBROOK, I.D. Plasma and salivary p h a r m a c o k i n e t i c s of caffeine in man. Eur. J. Clin. Pharmacol. 2__!:45-62, 1981. .,
~
20. PAILLARD, F., ARDAILLOU, R., MALENDIN, H., FILLASTRE, J-P., PRIER, S. Renal effects of salmon calcitonin in man. !. Lab. Clin. Med. 80:200-216, 1972. 21. AGUS, Z., GARDNER, L.B., BECK, L.H., GOLDBERG, M. Effects of parathyroid hormone on renal tubular reabsorption of calcium, sodium and phosphate. Am. J. Physiol. 224:1143-1148, 1973. 22. PARSONS, S.R., NADEAU, M.H. Physiological effects of caffeine in the rat: E x t r a c e l l u l a r cyclic AMP status, growth pattern and glucose m e t a b o l i s m in adipose tissue. ~. Nutr. 111:658-664, 1981. 23. WACHMAN, A., HATTNER, R.S., GEORGE, B., BERNSTEIN, D,S. Effects of d e c a f f e i n a t e d and n o n d e c a f f e i n a t e d coffee ingestion on blood glucose and plasma r a d i o i m m u n o r e a c t i v e insulin responses te rapid intravenous infusion of glucose in normal man. MetabQlism i__99:539-546, 1970. 24. RAPTIS, S., VON BERGER, L., DOLLINGER, J.G., PFEIFFER, E.F. Influence of ethanol, intragastric cooling on gastrin and insulin Nutr. Metabol. 17:352-359, 1974.
H.C., GOSTOMYZK, caffeine and secretion in man.
25. BELLET, S., ROMAN, L. DECASTRO, KIM, K.E,, KERSHBAUM, A. Effect of coffee ingestion on c a t e c h o l a m l n e release. Metabolism 18:288-291, 1969. 26. ROBERTSON, D., WADE, D., WORKMAN, R., WOOSLEY, R,L., OATES, J.A. Tolerance to the humoral and hemodynamic effects of caffeine in man. ~. Clin. Invest. 67:1111-1117, 1981.
Accepted for publication November 10, 1983.
THE
E F F E C T OF D I E T A R Y MAGNESIUM, SODIUM
C A F F E I N E ON U R I N A R Y E X C R E T I O N OF C A L C I U M , AND P O T A S S I U M IN H E A L T H Y Y O U N G F E M A L E S
L i n d a K. M a s s e y , PhD, and K e v i n J. W i s e , BS Food S c i e n c e and H u m a n N u t r i t i o n , W a s h i n g t o n S t a t e U n i v e r s i t y , P u l l m a n , WA 9 9 1 6 4 - 2 0 3 2
ABSTRACT Twelve female college students drank decaffeinated c o f f e e or tea to w h i c h O, 150 or 300 mg c a f f e i n e had been added. Each s u b j e c t had f a s t e d at l e a s t ten h o u r s b e f o r e d r i n k i n g e a c h of the t h r e e test b e v e r a g e s . U r i n e s a m p l e s w e r e c o l l e c t e d at one, two and three h o u r s after c a f f e i n e c o n s u m p t i o n . Total u r i n a r y t h r e e hour e x c r e t i o n of c a l c i u m , m a g n e s i u m and s o d i u m , but not p o t a s s i u m , i n c r e a s e d s i g n i f i c a n t l y after c a f f e i n e intake. The i n c r e a s e d o u t p u t of c a l c i u m and s o d i u m was m a i n l y due to s i g n i f i c a n t l y i n c r e a s e d u r i n a r y c a l c i u m and s o d i u m c o n c e n t r a t i o n s , w h i l e the i n c r e a s e d o u t p u t of m a g n e s i u m a p p e a r e d to be due to the c o m b i n a t i o n of both a slightly increased urinary magnesium c o n c e n t r a t i o n and v o l u m e . Total urine volume c o r r e l a t e d s i g n i f i c a n t l y w i t h d o s e of c a f f e i n e per b o d y w e i g h t when 300 mg of c a f f e i n e was c o n s u m e d . The e f f e c t s of c a f f e i n e on m i n e r a l e x c r e t i o n w e r e p r i m a r i l y due to c h a n g e s in m i n e r a l c o n c e n t r a t i o n and i n c r e a s e d u r i n a r y v o l u m e at one and two h o u r s .
KEY
WORDS:
Caffeine, potassium
urine,
calcium,
magnesium,
sodium,
INTRODUCTION D i e t a r y s u r v e y s have shown that the m a j o r i t y of the U.S. population consume caffeine-containing b e v e r a g e s daily, i n c l u d i n g all age g r o u p s (I,2). In a d d i t i o n to its well k n o w n s t i m u l a t o r y e f f e c t s on the c e n t r a l n e r v o u s s y s t e m , c a f f e i n e a f f e c t s a wide v a r i e t y of o t h e r t i s s u e s and o r g a n s , i n c l u d i n g the k i d n e y , w h e r e c a f f e i n e has a weak d i u r e t i c e f f e c t (1,3). The only p r e v i o u s study on the e f f e c t s of m e t h y l x a n t h i n e s on u r i n a r y m i n e r a l e x c r e t i o n found that in the s i n g l e s u b j e c t g i v e n an u n s p e c i f i e d i n j e c t e d dose of t h e o p h y l l i n e , u r i n a r y o u t p u t of c a l c i u m , m a g n e s i u m , s o d i u m and p o t a s s i u m i n c r e a s e d (4). Since o t h e r d i u r e t i c s are k n o w n to e f f e c t c a l c i u m and m a g n e s i u m e x c r e t i o n as w e l l as s o d i u m and p o t a s s i u m (5,6), it s e e m e d l o g i c a l to investigate caffeine. R e c e n t l y , H e a n e y and R e e k e r (7) r e p o r t e d that c a f f e i n e c o n s u m p t i o n c o r r e l a t e d w i t h a d e c r e a s e d c a l c i u m b a l a n c e in p r e m e n o p a u s a l f e m a l e s by i n c r e a s i n g both u r i n a r y and intestinal calcium losses. 43
44
MASSEY AND WISE: CAFFEINE AND URINARY MINERALS METHODS
T w e l v e h e a l t h y f e m a l e s , ages 2 2 - 3 0 y e a r s (mean 24.5 years) were r e c r u i t e d from s e n i o r and g r a d u a t e c l a s s e s at Washington State University. All s u b j e c t s w e r e w i t h i n 10% of i d e a l body w e i g h t and no s m o k e r s w e r e i n c l u d e d , s i n c e s m o k i n g i n c r e a s e s c a f f e i n e c l e a r a n c e (8). I n f o r m e d c o n s e n t was c o l l e c t e d a c c o r d i n g to h u m a n s u b j e c t r i g h t s p r o c e d u r e s of Washington State University. On t h r e e s e p a r a t e m o r n i n g s at one week i n t e r v a l s , each s u b j e c t d r a n k one of t h r e e b e v e r a g e s w h i c h r a n d o m l y c o n t a i n e d e i t h e r 150mg, 3 0 0 m g or no c a f f e i n e . The c a f f e i n e was w e i g h e d s e p a r a t e l y and a d d e d to a b e v e r a g e base w h i c h did not c o n t a i n caffeine. Ten s u b j e c t s chose d e c a f f e i n a t e d c o f f e e , one decaffeinated tea and one h e r b a l tea. Each s u b j e c t r e c e i v e d the same b e v e r a g e base all t h r e e e x p e r i m e n t a l days. Each s u b j e c t f a s t e d for at l e a s t ten h o u r s b e f o r e c o n s u m i n g the test b e v e r a g e , a l t h o u g h w a t e r was p e r m i t t e d ad l i b i t u m . Each s u b j e c t was asked not to c h a n g e e x e r c i s e or e a t i n g p a t t e r n s in the day b e f o r e each treatment. The e x p e r i m e n t was d e s i g n e d to r e s e m b l e the d i e t a r y p a t t e r n of b r e a k f a s t s k i p p i n g , w i t h the s u b s t i t u t i o n of a caffeine-containing b e v e r a g e for the m o r n i n g m e a l . The e x p e r i m e n t a l p r o c e d u r e was m o d e l e d a f t e r that of A l l e n et al. (9). Each s u b j e c t e m p t i e d her b l a d d e r , then d r a n k 240 ml of the test b e v e r a g e c o n t a i n i n g a b l i n d e d , r a n d o m - o r d e r e d , a m o u n t of c a f f e i n e or no c a f f e i n e . At one, two and t h r e e hours, e a c h s u b j e c t e m p t i e d her b l a d d e r , c o l l e c t i n g all u r i n e p r o d u c e d . U r i n e p r o d u c t i o n at all time p o i n t s was e n h a n c e d by h a v i n g each s u b j e c t d r i n k an a d d i t i o n a l 240 ml of d i s t i l l e d w a t e r at h o u r s one and two. The s u b j e c t s were o n l y a l l o w e d m i n i m a l p h y s i c a l m o v e m e n t and m o s t of the s u b j e c t s read or s l e p t d u r i n g the three-hour experimental period. U r i n e v o l u m e s w e r e m e a s u r e d , then c o n c e n t r a t e d HC1 (5% v o l : v o l ) was a d d e d . U r i n e s a m p l e s were f r o z e n u n t i l analy'zed. All g l a s s w a r e used for c o l l e c t i n g , m e a s u r i n g , s t o r i n g or a n a l y z i n g s a m p l e s was a c i d - w a s h e d and r i n s e d in d e i o n i z e d distilled water. C a l c i u m and m a g n e s i u m w e r e d e t e r m i n e d u s i n g a t o m i c a b s o r p t i o n s p e c t r o s c o p y on a l i q u o t s d i l u t e d in l a n t h i u m o x i d e c a r r i e r s , w h i l e s o d i u m and p o t a s s i u m were d e t e r m i n e d u s i n g f l a m e p h o t o m e t r y of u n d i l u t e d a l i q u o t s . S a m p l e s of HCI and w a t e r s used for the e x p e r i m e n t were a n a l y z e d and d e t e r m i n e d not to have d e t e c t a b l e a m o u n t s of t h e s e m i n e r a l s . H a b i t u a l c a f f e i n e c o n s u m p t i o n of each s u b j e c t from all b e v e r a g e s and m e d i c a t i o n s was d e t e r m i n e d by q u e s t i o n n a i r e . C a f f e i n e c o n t e n t of b e v e r a g e s and m e d i c a t i o n s was c a l c u l a t e d f r o m the v a l u e s of P e n n i n g t o n and C h u r c h (10). C o n s u m p t i o n of c h o c o l a t e and o t h e r c o c o a p r o d u c t s was not d e t e r m i n e d s i n c e the predominant methylxanthine in c o c o a p r o d u c t s is t h e o b r o m i n e (11), w h i c h has very l i t t l e d i u r e t i c or s t i m u l e n t e f f e c t (12). One way a n a l y s i s of v a r i a n c e was used to a n a l y z e the e f f e c t of c a f f e i n e c o n s u m p t i o n on t o t a l and h o u r l y u r i n e v o l u m e s , u r i n e ion c o n c e n t r a t i o n s and ion e x c r e t i o n . Linear regression was used to a n a l y z e the r e l a t i o n s h i p b e t w e e n c a f f e i n e dose per
MASSEY AND WISE: CAFFEINE AND URINARY MINERALS body weight and water and ion e x c r e t i o n . between low users and moderate users were t-test.
45
Potential d i f f e r e n c e s d e t e r m i n e d using a
RESULTS Caffeine c o n s u m p t i o n had only a weak, n o n - s i g n i f i c a n t , d i u r e t i c effect (Table i), However urinary c o n c e n t r a t i o n s of sodium and calcium almost doubled after the higher caffeine dose (Table i). Urinary m a g n e s i u m and p o t a s s i u m c o n c e n t r a t i o n did not change s i g n i f i c a n t l y .
TABLE 3 Hour
Urine
Volume
(ml)
CALCIUM
(mg/l)
MAGNESIUM SODIUM
(mg/l)
(mg/l)
POTASSIUM ~ean
(mg/l)
• standard
and Mean
Mineral
Caffeine dose 150
0 URINE
i. Concentration
(mg) 300
F
p
463•
525•
626•
1.49
N.S.
43.8•
54.2•
74.2•
3.9
25.1•
30.0•
28.9•
1.09
N.B.
103•
175•
198•
5.59
<.025
112•
139•
108•
0.40
N.S.
<
.05
deviation
Total urinary e x c r e t i o n of calcium and sodium more than doubled due to the combined effect of increased c o n c e n t r a t i o n and volume (Table 2). Total m a g n e s i u m e x c r e t i o n increased 50% due to the combined effect of increased c o n c e n t r a t i o n and volume. The increased p o t a s s i u m e x c r e t i o n was entirely due to i n c r e a s e d urine volume and was not s i g n i f i c a n t l y d i f f e r e n t after caffeine consumption.
TABLE 3 Hour
0 CALCIUM
(mg)
MAGNESIUM SODIUM
(mg)
POTASSIUM ~Mean
(mg)
(mg)
Total
2.
Mineral
Caffeine dose 150
Excretion * F
(mg)
p
30O
18.7•
27.2•
45.3•
7.41
< .005
i0.3~4.1
11.7•
15.2•
3.52
<.05
467•
812•
1133•
9.77
<.oo5
454•
490•
599•
1.90
N.S.
• standard
deviation
46
MASSEY AND WISE: CAFFEINE AND URINARY MINERALS
T o t a l u r i n e v o l u m e for each s u b j e c t c o r r e l a t e d significantly with the dose of c a f f e i n e c o n s u m e d per kg b o d y w e i g h t at the h i g h e s t dose of c a f f e i n e (r= - 0 . 7 3 , p < . 0 5 ) . H o w e v e r , t h e r e was no c o n s i s t e n t d o s e - d e p e n d e n t e f f e c t on t o t a l e x c r e t i o n of any ion. U r i n e v o l u m e did not d i f f e r s i g n i f i c a n t l y over the t h r e e hour e x p e r i m e n t a l o b s e r v a t i o n at any c a f f e i n e dose, nor did u r i n e v o l u m e d i f f e r s i g n i f i c a n t l y with caffeine dose at any of the h o u r l y c o l l e c t i o n s ( F i g u r e 1). C a f f e i n e had its g r e a t e s t e f f e c t on c a l c i u m c o n c e n t r a t i o n at one hour a f t e r its c o n s u m p t i o n ( F i g u r e i), and at both one and two h o u r s c a l c i u m c o n c e n t r a t i o n s were significantly (p < . 0 5 ) r e l a t e d to c a f f e i n e d o s e . A f t e r the c o n s u m p t i o n of 300 mg caffeine, calcium concentrations declined significantly (p < . 0 2 5 ) b e t w e e n one and t h r e e h o u r s . At the th i r d h o u r , c a l c i u m concentrations were not s i g n i f i c a n t l y d i f f e r e n t i r r e g a r d l e s s of caffeine dose. T o t a l c a l c i u m e x c r e t i o n at each h o u r l y s a m p l e p o i n t was s i g n i f i c a n t l y r e l a t e d to the c a f f e i n e dose (p < . 0 2 5 ) . Sodium concentration and t o t a l s o d i u m o u t p u t c l o s e l y p a r a l l e l e d that of c a l c i u m , and b o t h d i f f e r e d s i g n i f i c a n t l y (p < . 0 2 5 ) w i t h c a f f e i n e dose at h o u r s one and two. M a g n e s i u m and p o t a s s i u m concentrations did not c h a n g e s i g n i f i c a n t l y due to c a f f e i n e consumption, although decreased concentrations w e r e seen at h o u r s one and two at all c a f f e i n e loads, p o s s i b l y due to a water-induced diuresis. Five of the s u b j e c t s h a b i t u a l l y c o n s u m e d l o w a m o u n t s of c a f f e i n e , only 13-85 mg d a i l y , w h i l e seven s u b j e c t s h a b i t u a l l y c o n s u m e d a v e r a g e a m o u n t s , b e t w e e n 230 and 435 mg d a i l y . When d a t a was a n a l y z e d for t h e s e two s u b g r o u p s , the m o d e r a t e c a f f e i n e u s e r s did not s h o w c o n s i s t e n t l y l o w e r i n c r e a s e s in total ion excretion, s u g g e s t i n g that they had not d e v e l o p e d t o l e r a n c e to the r e n a l e f f e c t s of c a f f e i n e . Further study with larger populations and a g r e a t e r r a n g e of i n t a k e s is n e e d e d b e f o r e the p o s s i b i l i t y of t o l e r a n c e can be r u l e d out.
DISCUSSION In this small s a m p l e of y o u n g h e a l t h y w o m e n , c a f f e i n e consumption i n c r e a s e d u r i n a r y l o s s e s of c a l c i u m , m a g n e s i u m and sodium. The a m o u n t of c a f f e i n e n e e d e d to s h o w t h e s e e f f e c t s was not l a r g e , i n d e e d the h i g h e s t dose used, 300 mg, was the a v e r a g e a m o u n t c o n s u m e d d a i l y by t h e s e s u b j e c t s . In the r e c e n t USDA food consumption s u r v e y (2), d i e t a r y i n t a k e s of c a l c i u m and m a g n e s i u m did not m e e t the R e c o m m e n d e d D i e t a r y A l l o w a n c e s for y o u n g w o m e n . T h e r e is i n c r e a s i n g c o n c e r n that l i f e l o n g s u b o p t i m a l c a l c i u m s t a t u s may p r e d i s p o s e a d u l t s to the d e v e l o p m e n t of o s t e o p o r o s i s in l a t e r y e a r s (13, 14). Similarly marginal magnesium status has been s u g g e s t e d to be a c o n t r i b u t i n g f a c t o r for both bone loss and c a r d i o v a s c u l a r d i s e a s e (15). H e a n e y and R e c k e r (7) r e p o r t e d that c o n s u m p t i o n of c a f f e i n e - c o n t a i n i n g beverages varied i n v e r s e l y w i t h the c o n s u m p t i o n of d a i r y p r o d u c t s , w h i c h are e x c e l l e n t s o u r c e s of d i e t a r y c a l c i u m and m a g n e s i u m . Thus, a d i e t a r y p a t t e r n of h i g h c a f f e i n e c o n s u m p t i o n in c o m b i n a t i o n w i t h a low c a l c i u m and m a g n e s i u m i n t a k e may s t r e s s the h o m e o s t a t i c mechanisms maintaining c a l c i u m and m a g n e s i u m s t o r e s .
MASSEY AND WISE: CAFFEINE AND URINARYMINERALS
47
20"
~%~
OMG | 150MG A 300 MG
~
T I & "~
15,
Z L,u
~
10~
s
m Z
s
10"
8 |
-~.~,
250-
200-
150.
100" !
2 HOURS
FIG.1 Mean hourly calcium excretion, urine calcium concentraitons and urine volumes of twelve healthy young adult females after consuming both doses of caffeine, and the control decaffeinated beverage.
48
MASSEY AND WISE: CAFFEINE AND URINARY MINERALS
If the c a f f e i n e s o u r c e in the d i e t is c o f f e e , m a g n e s i u m l o s s e s due to c a f f e i n e may be small c o m p a r e d to the m a g n e s i u m c o n t e n t of the c o f f e e c o n s u m e d , w h i c h is 16 mg per 8 oz. cup (10). A c c o r d i n g to the USDA survey data, a d u l t s 23 years and o l d e r d e r i v e d 12 to 21% of their d i e t a r y m a g n e s i u m from the n o n a l c o h o l i c b e v e r a g e group, m a i n l y from c o f f e e (2). However, a l t h o u g h c o f f e e is a good s o u r c e of d i e t a r y m a g n e s i u m , it only c o n t a i n s 5 mg c a l c i u m per 8 oz. cup (10). I n c r e a s e s in u r i n a r y c a l c i u m and m a g n e s i u m do not n e c e s s a r i l y c a u s e d e p l e t i o n of body t i s s u e s t o r e s of these minerals. I n c r e a s i n g s o d i u m c o n s u m p t i o n from 75 to 240 meq d a i l y i n c r e a s e d u r i n a r y c a l c i u m o u t p u t from 110 to 167 mg, but i n t e s t i n a l a b s o r p t i o n i n c r e a s e d from 39% to 49%, w h i c h c o m p e n s a t e d for the i n c r e a s e d u r i n a r y c a l c i u m e x c r e t i o n (18). H o w e v e r , H e a n e y and R e c k e r (7) found that i n c r e a s e d c a f f e i n e c o n s u m p t i o n c o r r e l a t e d w i t h i n c r e a s e d fecal c a l c i u m loss as well. Several other dietary components, including protein (5,7,17), a l c o h o l (5) and g l u c o s e (5,18) i n c r e a s e u r i n a r y c a l c i u m e x c r e t i o n , as well as c a f f e i n e and s o d i u m , so some i n d i v i d u a l s may not be able to c o m p e n s a t e for the a d d i t i o n a l u r i n a r y l o s s e s c a u s e d by c a f f e i n e . I n c r e a s e s in u r i n a r y m i n e r a l e x c r e t i o n w e r e g r e a t e s t at one hour, then fell in the f o l l o w i n g two hours. A f t e r oral c o n s u m p t i o n of 300 mg c a f f e i n e , s e r u m c o n c e n t r a t i o n s peak one hour later, but d e c l i n e s l o w l y since c a f f e i n e has an a v e r a g e h a l f - l i f e of three to four hours (19). T h e r e f o r e , the r e l a t i v e l y r a p i d r e t u r n to usual m i n e r a l c o n c e n t r a t i o n s and t o t a l e x c r e t i o n are not l i k e l y to be due to d e c r e a s e s in c a f f e i n e c o n c e n t r a t i o n s . S t u d i e s c o m p a r i n g the r e s p o n s e of n o r m a l and h y p o p a r a t h y r o i d men to c a l c i t o n i n i n f u s i o n s u g g e s t that these s e c o n d a r y d e c r e a s e s could be m e d i a t e d by p a r a t h y r o i d h o r m o n e (20). P a r a t h y r o i d h o r m o n e , w h i c h in h u m a n s d e c r e a s e s net c a l c i u m e x c r e t i o n , a p p e a r s to act by e l e v a t i n g cAMP l e v e l s in the tubule (21). High d o s e s of m e t h y l x a n t h i n e s , i n c l u d i n g c a f f e i n e , e l e v a t e i n t r a c e l l u l a r cAMP l e v e l s by i n h i b i t i n g p h o s p h o d i e s t e r a s e . H o w e v e r , rats g i v e n 8.69 m g / k g c a f f e i n e for four weeks, a h i g h e r dose than our s u b j e c t s r e c e i v e d , had no s i g n i f i c a n t c h a n g e s in e i t h e r p l a s m a or u r i n a r y c A M P l e v e l s (22). The s t u d y by Agus et al (21) also s u g g e s t s that the u r i n a r y e f f e c t s o b s e r v e d in this study are p r o b a b l y not m e d i a t e d by cAMP. They fed d i b u t y r y l c y c l i c a d e n o s i n e m o n o p h o s p h a t e dogs, and found d i b u t y r y l cAMP d e c r e a s e d total u r i n a r y c a l c i u m , even t h o u g h c a l c i u m and s o d i u m r e s o r p t i o n was i n h i b i t e d in the p r o x i m a l tubule. Thus the e f f e c t s of c a f f e i n e o b s e r v e d in this s t u d y are not c o n s i s t e n t w i t h the e f f e c t of c a f f e i n e a c t i n g s o l e l y to i n h i b i t p h o s p h o d i e s t e r a s e , thus e l e v a t i n g i n t r a c e l l u l a r c A M P l e v e l s in the r e n a l t u b u l e . I n s u l i n , like c a f f e i n e , i n c r e a s e s net c a l c i u m e x c r e t i o n . H o w e v e r , i n s u l i n d e c r e a s e s , not i n c r e a s e s , s o d i u m e x c r e t i o n (8). Both W a c h m a n et al (23) and R a p t i s et al (24) r e p o r t e d that n e i t h e r blood g l u c o s e nor s e r u m i n s u l i n was e l e v a t e d f o l l o w i n g c a f f e i n e c o n s u m p t i o n , so it seems u n l i k e l y that the i n c r e a s e d u r i n a r y s e c r e t i o n of m i n e r a l s is s e c o n d a r y to an i n s u l i n elevation. I n t e r e s t i n g l y , c a f f e i n e ' s e f f e c t s are s i m i l a r to t h o s e of s a l m o n c a l c i t o n i n in man (20). C a f f e i n e c o n s u m p t i o n i n c r e a s e s u r i n a r y c a t e c h o l a m i n e o u t p u t (25, 26), so c a f f e i n e ' s
MASSEY AND WISE: CAFFEINE AND URINARY MINERALS
49
renal effects could be mediated by the s y m p a t h e t i c nervou~ system. Another u n e x p l o r e d p o s s i b i l i t y is that p r a s t a g l a n d i n s may be the p h y s i o l o g i c a l agents. Further work is needed to d e t e r m i n e the m e c h a n i s m s actually involved.
ACKNOWLEDGMENTS This research Project 0457,
was supported by the A g r i c u l t u r a l Re~ear~h Center, Wash. State Univ. S c i e n t i f i c paper NQ~ 6558.
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50
MASSEY AND WISE: CAFFEINE AND URINARY MINERALS
13. AVIOLI, L.V. Postmenopausal osteoporosis: cure. Fed. Proc. 40:2418-2422, 1981. 14. SEEMAN, the elderly.
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in
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16. BRESLAU, N.A., MCGUIRE, J.L., ZERWEKH, J.E., PAK, C.Y.C. The role of dietary sodium on renal excretion and intestinal absorption of calcium and on vitamin D metabolism. 2" C~in. Endocrin. Metab. 55:369-373, 1982. 17. ALTCHULER, S.I. Nutr. Res. 2:193-200,
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~
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Accepted for publication November 10, 1983.