Kunihiko ISHITANI, Eiko ITAKURA Shiro GOTO
and Takatoshi ESASHI
1
Higashi Sapporo Hospital, Sapporo 003-8585, Japan 1
Formerly, Tokyo University of Agriculture, Ichikawa 272-0035, Japan
3 Division of Applied Food Research, The National Institute of Health
and Nutrition, Tokyo 162-8636, Japan
(Received
September 20. 1998)
Summary Recent
dietary life involves frequent opportunities for the ingestion of
purified, processed food products and preserved foods, and it has been
pointed out that the current dietary mineral intake strongly tends
toward nutritional imbalance. The
Ryukyu Islands
yield coral which contains calcium and magnesium in a content ratio of
about 2 to I, with their approximate contents of 20 and 10%,
respectively. In this report, the calcium absorption from the
ingestion of crackers into which the coral powder was incorporated
(coral-added crackers) and that from ingestion of calcium
carbonate-added crackers was comparatively assessed. Twelve healthy
adult volunteers (6 men and 6 women) ingested coral-added crackers
(calcium content: 525 mg) and calcium carbonate-added crackers (ditto)
once each alternately on a cross-over design with a wash-out period of
3 d between the regimens. The study also included controls receiving
neither cracker. The degree of intestinal absorption of calcium from
coral-added crackers and that from calcium carbonate-added crackers
was evaluated in terms of increment in urinary calcium excretion per
dL of glomerular filtrate (GF) (difference between coral calcium and
calcium carbonate) and increase in urinary calcium excretion per
milligram creatinine (difference from control value). The increment in
urinary calcium excretion per dL of GF during the latter half of the
observation period after the ingestion of coral-added crackers was
significantly greater than that during the latter half of the
observation period after ingestion of calcium carbonate-added crackers
(p =0.039, paired t-test). A significant difference
(from control value) in the increase of urinary calcium excretion per
milligram creatinine was also observed (p = 0.0008). The
present data, though from a relatively few study subjects, suggest
that the calcium of coral origin is better absorbed from the intestine
than calcium of calcium carbonate origin on the average.
Key
Words coral calcium, calcium absorption, urinary calcium excretion
According to
the Proposed Diagnostic Criteria for Osteoporosis (Japanese Society
for Bone Metabolism) (1), as many as roughly ten million Japanese
persons are estimated to be diagnosed as having osteoporosis, which
thus is the most common disease ill Japan.
A
therapeutic or prophylactic approach to osteoporosis, or to
suppression of decrease in bone mass, is calcium supplementation. The
underlying mechanism is generally thought to consist in the
suppression of parathyroid hormone secretion (2). Recently, stress is
laid particularly on the importance of a well-balanced supply of
calcium and magnesium rather than simple calcium intake (3).
In
their epidemiological study on the relationship of cardiac disorders
to calcium/magnesium intake ratio in 1940, Karppanen et al (4) pointed
out that the number of patients with cardiac disorder was prone to
increase with rising calcium/magnesium ratio. Additionally, cardiac
disorders were found to be of the highest in incidence in
Finland
where the intake ratio exceeded 4: 1.
It
has also been demonstrated by Seelig et al (5) in
a balance test with a daily magnesium intake of350mg and a
progressively increasing daily calcium intake of 200 to 1,400 mg
that urinary magnesium excretion increased with increasing calcium
intake, leading eventually to a negative balance with excessive
magnesium excretion over its actual intake. The nutritional
requirement for calcium is 600 mg a day and the recommended daily
magnesium intake is 300mg in
Japan
. It may thus be said that a
calcium:magnesium intake ratio of 2: 1 is advisable for Japanese (6).
Ryukyuan
coral is a dietary material approved as a food additive that contains
calcium and magnesium in an approximate ratio of 2: 1, with their
contents of 20 and 10%, respectively. Under the view that it is
justified to add this foodstuff to the so-called nutritionally
well-balanced foods which satisfy the mineral balance, we incorporated
coral powder into inexpensive, light, tasty crackers. This foodstuff
was incorporated into crackers to permit a well-balanced mineral
intake of about half the daily requirements of .calcium and magnesium
(i.e., 300 mg calcium and 150 fig magnesium) by the daily ingestion of
4 crackers (per box) as a snack.
This
study was undertaken to evaluate in humans whether mean intestinal
absorption of coral-derived calcium incorporated into crackers (h~reinafter
referred to as coral-added crackers) might be comparable or even
superior to mean intestinal absorption of calcium carbonate-derived
calcium in crackers.
METHODS
Subjects. Twelve
normal subjects (6 men and 6 women; their ages, body weights and
heights shown in Table I) participated in the study after giving
written informed consent. The study was designed in accordance with
the spirit of the De- claraltion of Helsinki (adopted in 1964; as
amended in 1989) (7) and conducted after review ,l!1d approval by the
Higashi Sapporo Hospital Institutional Review Board.
None of the subjects had a history of bone disease, peptic ulcer,
enterectomy, regional enteritis, malabsorption, nephrolithiasis, liver
cirrhosis, or renal disorder. The
subjects
had not taken calcium supplements or vitamin D preparations, nor
received anticonvulsants, diuretics, adrenocorticosteroids, estrogens
or any other drugs .that could affect calcium metabolism during the
month preceding the start of the study.
Methods.
The subjects were divided
into two groups; subjects of one group ingested coral-added crackers
first (group A) and those of the other group ingested calcium
carbonate-added crackers first (group B). After a subsequent 3-d
wash-out period, the groups received the study regimens on a
cross-over design. An additional group (group C) served as a control
not ingesting crackers. In order to sharpen calcium absorption, all
study subjects were so instructed as to adhere to a daily diet
restricted in calcium (300 mg/d, corresponding to half the dietary
allowance), magnesium (150mg/d, corresponding to half the aimed
intake) and sodium (2.3 g/d, corresponding to half the dietary
allowance) beginning 2 d prior to the start of study regimens.
Each
12-g piece of coral-added cracker contained 75 mg of calcium and 36 mg
of magnesium. Calcium and magnesium contents of a 12-g calcium
carbonate-added cracker were 75 and 6mg, respectively. Each subject
ingested seven pieces of either cracker each time in this study since,
according to Harvey et al (8), oral ingestion of 500 mg of calcium
suffices for adequate evaluation of intestinal calcium absorption by
measurements of urinary calcium excretion. The calcium intake and
magnesium intake after the ingestion of 7 coral:. added crackers were
calculated to be 525 and 252 mg, respectively, and those after
ingestion of 7 calcium carbonate-added crackers to be 525 and 42 mg,
respectively.
Controls
(group C) did not ingest either cracker at all. During each phase of
the study, all subjects fasted from
8:00p.m.
of the
preceding day, but were allowed to drink 300mL of distilled
water at 8:00 and 11 :00 p.m. of that day and 600 mL of distilled
water at 6:00 a.m. of the test day.
A
2-h urine collection was obtained from each subject from
6:00
to
8:00 a.m.
(2 h pre-ingestiori). At
8:00 a.m.
, subjects of group A ingested an initial regimen consisting of
coral-added crackers and those of group g ingested an initial regimen
consisting of calcium carbonate crackers, with 300 mL of distilled
water. Another 2-h urine collection was then obtained from
8:00
to
10:00 a.m.
(first half of observation period). At
10:00 a.m.
, each subject drank 300 mL of distilled water and urine was collected
for 2 h from
10:00 a.m.
to
noon
(latter half of observation period). An additional 2-h collection from
noon
to
2:00 p.m.
was also obtained for reference. Controls of group C ingested
distilled water alone at these time points, each followed by 2-h urine
collection (i.e.,
08:00-10:00
and
10:00-12:00
).
Procedure
for evaluation of calcium absorption. In this study, the calcium
absorption from the intestinal tract was evaluated on the basis of
urinary calcium excretion as reported by Harvey et al (8), Nicar and
Pak (9), Pak et al (10), Broadus et al (11), Birge et al (12), and
Dokkum et al (13). Particularly, for comparative assessments of the
absorption of calcium from coral-added crackers versus that from
calcium carbonate-added crackers, measurements were carried out with
the following five assay methods of Nicar and Pak and Harvey et al.
Method I) Urinary calcium excretion (in mg) per milligram of
creatinine during the first 4 h post-ingestion from 8:00 a.m. to noon.
Method 2) Increment in urinary calcium excretion (in mg) per dL of OF
during the latter half of the observation period, calculated by
subtracting pre-ingestion urinary calcium excretion (
6:00-8:00 a.m.
) from post-ingestion urinary calcium excretion (
10:00 a.m.
-
noon
). Method 3) Increment in urinary calcium excretion (in mg) per dL of
OF during the first half of the observation period, calculated by
subtracting from post-ingestion urinary calcium excretion (
8:00-10:00 a.m.
). Method 4) Urinary calcium excretion (in mg) calculated by
subtraction of the urinary calcium excretion per milligram creatinine
in non-cracker-ingested controls over 4 h, from
8:00 a.m.
to
noon
, from post-ingestion urinary calcium excretion per milligram
creatinine during 4 h, from
8:00 a.m.
to
noon
. Urinary calcium excretion in mg/dL of OF was calculated by
multiplying urinary calcium excretion (in mg) per milligram urinary
creatinine by serum creatinine concentration (in mg/dL). (Blood
collection was performed at 8;00 a.m. just prior to cracker ingestion
and at
noon
(i.e., 2 h post-ingestion), and serum creatinine levels determined at
these time points were used for the calculation.) Method 5) Determine
the increase in serum calcium concentration (in mg/dL) by subtracting
the serum calcium concentration in non-cracker-ingested controls from
post-ingestion serum calcium concentration. Similar procedures were
used for the evaluation of magnesium absorption. Inter-group
comparisons were made using a paired. t-test.
Urine
samples were analyzed for calcium by the OCPC method ("Jisseiken"
Ca, an auto analyzer system reagent; DIA-Iatron Co., Ltd., Tokyo,
Japan), and for magnesium by the xylidyl blue method ("Jisseiken"
Mg, an auto analyzer system
Coral-Oerived
Calcium Absorption by Humans
Table
2. Calcium
absorption from the intestine and serum calcium collcci1trutioll
following ingestion of calcium-supplemented crackers.
RESULTS
Calcium absorption Pertinent data are presented in Table 2. The
group receiving coral-added crackers and that receiving calcium
carbonate-added crackers were practically comparable with respect to
urinary calcium excretion during 2-h pre-ingestion (
6:00-8:00 a.m.
). Mean urinary calcium excretion after the ingestion of coral-added
crackers was greater than that after calcium carbonate-added crackers
by four determination methods, I) through 4). Significant intergroup
differences were noted in urinary calcium excretion (fig/fig Cr)
during 4-h post-ingestion (
8:00
-
noon
)
Vol
45, No 5, 1999
Table 3. Increase in
urinary calcium excretion (mg) per dL of glomerular filtrate during
the latter half of the observation period (
10:00 a.m.
-
noon
) after cracker ingestion in individual subjects.
by
Method I), increase in urinary calcium excretion (mg/dL OF) during the
latter half of the post-ingestion observation period (10:00 a.m. to
noon) by Method 2), and increase in urinary calcium excretion (A from
control~ mg/mg Cr) during 4-h post-ingestion (8:00 a.m. to noon) by
Method 4). However, Do significant difference was demonstrated for the
first half of the post-ingestion observation period (
8:00-10:00 a.m.
) by Method 3). These findings were
generally in line with the conclusions from absorption studies on
calcium citrate versus calcium carbonate by Harvey et al (8) and Nicar
and Pak (9) that calcium citrate was better absorbed.
The
increase in serum calcium concentration calculated by subtraction of
the control value from the post-ingestion serum calcium value (Method
5) also showed a significant difference between the two groups; hence,
a similar tendency to that reported by Harvey et al.
Individual
assay data for the latter half of the post-ingestion observation
period are presented in Table 3.
The
males exhibited a better calcium absorption from coral-derived calcium
as compared with the females, though the subject sample sizes were
small.
Meanwhile,
the increase in urinary calcium excretion during the subsequent 2-h
period (
noon
to
2:00 p.m.
), determined for reference, showed a
plateau with no
Coral-Derived
Calcium Absorption by Humans
Table
4. Increase in urinary magnesium excretion (mg) per dL of glomerular
filtrate and serum magnesium concentration during the latter half of
the observation period (IO:OOa.m.-noon) after cracker ingestion.
appreciable difference between the
two cracker regimens. It was thus considered appropriate to
assess the responses by analyzing two consecutive 2-h post-ingestion
urine samples for the comparison based on urinary calcium excretion.
Magnesium absorption
Intestinal
magnesium absorption and increases in serum magnesium concentration
following ingestion of the test crackers are shown in Table 4.
The
magnesium content of the coral-added cracker was as high as 252 mg
while that of the calcium carbonate-added cracker. was only 42 mg.
Significant intergroup differences were observed in respect of
increment in urinary magnesium excretion during the latter half of the
post-ingestion observation period (10:00 a.m. to noon) by Method 2) (p=0.001),
and there was an increase in serum magnesium concentration at noon
as compared to the serum magnesium value at 8:00 a.m. (p =
0.006).
DISCUSSION
The
assessments of calcium absorption from supplemented crackers performed
using five methods as described by Harvey et al (8) and Nicar and Pak
(9) demonstrated a better absorption of coral-derived calcium than
that of calcium carbonate-derived calcium on the average.
A
laboratory study in rats to explore the ability to utilize calcium
derived from Ryukyuan coral which contains calcium and magnesium at a
ratio of about 2-to-1 has been reported by Suzuki et al (14). The
investigators calculated the calcium balance from excretions in the
feces and urine during the last 3 d of a 4-wk rat feeding trial using
coral. They concluded that the efficiency of calcium utilization
was satisfactorily greater with coral-derived calcium as compared to
calcium
carbonate-derived calcium, although
the difference observed did not attain a level of statistical
significance.
Suzuki
et al also described that their concurrent test with a fivefold
increase in dietary magnesium intake (i.e., 0.25% as against 0.05%)
demonstrated a marked increase in urinary calcium excretion; hence, a
better calcium absorption in the group fed on high-magnesium (0.25%)
diet.
The
present study was conducted under conditions with a higher rate of
magnesium content (6-fold difference) as compared to the above two
laboratory studies of Suzuki et al, viz. a magnesium content of 36mg
(0.3%) per 12-g coral-added cracker versus a magnesium content of 6 mg
(0.05% ) per 12-g calcium carbonate-added cracker .
While
Suzuki et al have given no account of the high efficiency of calcium
utilization from coral in their article, it would be reasonable to
assume that the high magnesium content has some bearing upon the
intestinal absorption of calcium when viewed together with
consideration of the present human trial data. However , it is of
importance to mention that problems such as coral calcium solubility
in gastric acid, absorption from the intestine and reabsorption from
the renal tubules per se should be discussed. Additionally, the
potential involvement of magnesium and further basic studies are
needed .
The
present data demonstrating the remarkably good absorption of calcium
from coral containing calcium and magnesium in a ratio of 2-to-1 are
of profound interest, and it is anticipated that Ryukyuan coral can be
incorporated into a variety of inexpensive, light, tasty foods so as
to enable a ready dietary intake of calcium and magnesium in a ratio
of 2-to-l.
The
authors are gratefully indebted to Dr. Osamu Setoyama, Vice Director
of the Clinical Division,
Higashi
Sapporo
Hospital
, and dietitians and other staff of the
hospital for helpful discussion and expert cooperation throughout this
study.
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45, No 5, 1999
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