Minerals and Trace Elements
Effect of Dietary Caffeine and Theophylline on urinary
Calcium Excretion in the Adult Rat
SUSAN J. WHITING1 ANDHANNAH L WHFTNEY
Department of Home Economics, Mount Saint Vincent University, Halifax, Nova Scotia, Canada B3M 2J6
ABSTRACT The chronic effects of dietary caffeine or theophylline on urinary calcium excretion were investigated in the adult
male rat. When caffeine was added at two concentrations, 0.75 and 1.50 g/kg diet, 24-h urinary calcium excretion rose 300 and
450% on d 7, and 200 and 330% on d 14, respectively. There were no changes in the 24-h urinary excretion of phosphate,
sulfate, sodium and cAMP nor did urine volume change. The high dose of caffeine was compared to an equimolar dose of
theophylline ( 1.39 g/kg diet) in both Wistar and Sprague-Dawley rats. Urinary calcium excretion in theophylline-treated rats was
significantly greater than in caffeine-treated rats on all sampling days and in both strains of rat; the calciuric effect lasted at least
22 d. When rats were given indomethacin (3.3 mg/kg diet) the calciuria induced by caffeine and theophylline was abolished, and
sodium excretion in all groups was reduced by 35-50%, but urine volume was unchanged. The calciuria of methylxanthine
feeding may result from a prostaglandin-mediated process distinct from diuresis. J. Fiutr. 117: 1224-1228, 1987.
INDEXING KEY WORDS:
•calcium •caffeine •theophylline •indomethacin •calciuria
Caffeine, a common component of the human diet,
has recently been shown to influence calcium metab
olism in humans (1, 2). Caffeine intake was found to
be positively associated with urinary calcium excretion
in a study of dietary intakes and calcium balances of
perimenopausal women (1). The relationship between
caffeine and calcium excretion has also been directly
examined in a short-term (3-h) study of adults that
showed that urinary calcium excretion increased upon
administration of a single 300-mg dose of caffeine (2).
Because caffeine ingestion has been found to be signif
icantly correlated to a decrease in bone mineral content
of adult women (3), it is of special interest to explore
the relationship between caffeine ingestion and cal
cium metabolism.
The purpose of the experiments described in this pa
per was to examine the chronic effects on calcium ex
cretion of caffeine and theophylline ingestion in the
rat. It has been shown recently that rats injected with
large doses of caffeine demonstrate an elevated urinary
calcium excretion (4). We looked first at the effects of
feeding two doses of caffeine on urinary excretion of
calcium, sodium, phosphate, cyclic AMP and urine vol
ume. We then compared the effects of feeding caffeine
to those produced by feeding another methylxanthine,
theophylline, which is a more potent diuretic than caf
feine in the rat (5). Because prostaglandin production
is involved in methylxanthine-induced diuresis (5) and
in caffeine-induced calciuria found in human subjects
(6), we also administered the prostaglandin synthesis
inhibitor, indomethacin, to determine whether xan-
thine-induced calciuria is abolished in rats by blocking
prostaglandin formation.
MATERIALS AND METHODS
Animals. Male Wistar rats (Charles River, LaSalle,
Que.) were used in experiments 1 and 2. Male Sprague-
Dawley rats (Canadian Hybrid Farms, Kentville, NS)
were used in experiment 3. In all experiments, rats were
randomly assigned to one of three groups and housed
individually in wire-bottom metabolism cages with
lighting regulated to give a 12-h light-dark cycle. All
animals were acclimated to a control diet for 1 wk
before the collections. Food and water were provided
ad libitum throughout. Body weights and feed intakes
were recorded weekly and biweekly, respectively.
'Supported by giants from the Natural Sciences and Engineering
Research Council (NSERC) of Canada and from Mount Saint Vincent
University.
0022-3166/87 $3.00 ©1987 American Institute of Nutrition. Received 2 June 1986. Accepted 3 March 1987.
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