From the School of Public Health, Kaohsiung Medical College, Kaohsiung,
Taiwan, Republic of China.
Correspondence to Chun-Yuh Yang, School of Public Health, Kaohsiung Medical College, 100 Shih-Chuan 1st RD, Kaohsiung 80708, Taiwan, ROC. E-mail chunyuh{at}cc.kmc.edu.tw
Methods—All eligible cerebrovascular deaths (17 133 cases) of
Taiwan residents from 1989 through 1993 were compared with deaths from
other causes (17 133 controls), and the levels of calcium and
magnesium in drinking water of these residents were determined. Data on
calcium and magnesium levels in drinking water throughout Taiwan were
obtained from the Taiwan Water Supply Corporation. The control group
consisted of people who died from other causes, and the controls were
pair matched to the cases by sex, year of birth, and year of death.
Results—The adjusted odds ratios (95% confidence interval) were
0.75 (0.65 to 0.85) for the group with water magnesium levels between
7.4 and 13.4 mg/L and 0.60 (0.52 to 0.70) for the group with magnesium
levels of 13.5 mg/L or more. After adjustment for magnesium levels in
drinking water, there was no difference between the groups with
different levels of calcium.
Conclusions—The results of the present study show that there
is a significant protective effect of magnesium intake from drinking
water on the risk of cerebrovascular disease. This is an important
finding for the Taiwan water industry and human health.
In Taiwan, cerebrovascular disease is the third leading cause of deaths
for men and the second for women.12 The
age-adjusted mortality rate for cerebrovascular disease was 75.88 per
100 000 among men and 56.44 among women in 1995. In addition, there is
substantial geographic variation in cerebrovascular mortality within
the country. Such a geographic distribution may suggest an
environmental risk factor.
The hardness of drinking water is determined largely by its content of
calcium and magnesium. It is expressed as the equivalent amount of
calcium carbonate that could be formed from the calcium and magnesium
in solution.
Two theories have been offered concerning the causative agent
responsible for the relationship between death from
cardiovascular or cerebrovascular disease and water
hardness. Soft water is more corrosive than hard water and promotes the
dissolution of cadmium, lead, and other toxic substances from the
plumbing system into the drinking water.13
Another theory is that there is a protective effect from magnesium in
water.14 15 16
The former hypothesis could not be tested in his study because the
levels of lead and cadmium in drinking water were not available. The
objective of this study was to study the relationship between the
levels of calcium and magnesium in drinking water and death from
cerebrovascular disease in Taiwan.
Data on all deaths of Taiwan residents from 1989 through 1993 were
obtained from the Bureau of Vital Statistics of the Taiwan Provincial
Department of Health, which is in charge of the death registration
system in Taiwan. For each death, detailed demographic information,
including sex, year of birth, year of death, cause of death, place of
death (municipality), and residential district (municipality) were
recorded on computer tapes. The case group consisted of all
eligible cerebrovascular disease deaths occurring in people between 50
and 69 years of age (International Classification of Diseases,
9th Revision [ICD-9] codes 430 to 438). A control group was
formed that consisted of all other deaths with the exclusion of those
deaths that were associated with cardiovascular
disease. The deaths excluded were those caused by hypertensive disease
(ICD codes 401 to 405), ischemic heart disease (ICD codes 410
to 414), diseases of pulmonary circulation (ICD codes 415 to
417), other forms of heart disease (ICD codes 420 to 429),
cerebrovascular disease (ICD codes 430 to 438), and diseases of the
arteries, arterioles, and capillaries (ICD codes 440 to 448). Subjects
who died from gastric cancer (ICD code 151) were also excluded from the
control group because of a previously reported negative correlation
with hardness (calcium or magnesium) levels in drinking
water.17 Control subjects were pair matched to
the cases by sex, year of birth, and year of death. Each matched
control was selected randomly from the set of possible controls for
each case. Each case and its matched control had residence and place of
death in the same municipality. For controls, the most frequent causes
of death were diabetes mellitus (9.5%), liver cancer (9.3%), diseases
of the respiratory system (8.3%), lung cancer (8.0%), chronic liver
disease and cirrhosis (7.8%), and diseases of the genitourinary tract
(4.7%).
Information on the levels of calcium and magnesium in each
municipality's treated drinking water supply was obtained from the
Water Quality Research Center of Taiwan Water Supply
Corporation,18 to whom each waterworks is
required to submit drinking water quality data, including the levels of
calcium and magnesium. They also conduct routine water analyses
to assess the suitability of water for drinking from both the sources
and at various points in the distribution system. Four finished water
samples, one for each season, were collected from each waterworks. The
samples were then analyzed by the waterworks laboratory office
using standard methods. Since the laboratory office examines calcium
and magnesium levels on a routine basis using standard methods, it was
thought that the problem of analytical variability was minimal. Among
the 322 municipalities, 70 were excluded because they were supplied by
more than one waterworks and the exact population served by each
waterworks could not be determined. The final complete data consisted
of drinking water quality data from 252 municipalities.
Hardness (calcium and magnesium) remains reasonably constant for long
periods of time and is a quite stable characteristic of a
municipality's water supply.19 Some information
on the levels of water hardness was available for the study areas in
1980. The correlation between 1980 and 1990 hardness levels for the
study areas was reasonably high (r=.85). The waterworks in
each municipality received a questionnaire requesting information on
whether any changes had occurred in the water supply or the treatment
of the water during the past 20 years. No municipalities were excluded
because of changes in water quality (eg, the use of water softeners)
during the past few decades. It was believed that the hardness (calcium
and magnesium) levels in drinking water have remained reasonably
stable. We therefore assumed that calcium and magnesium levels in 1990
were a reasonable indicator of historical calcium and magnesium
exposure levels from drinking water. Data collected included the mean
levels of calcium and magnesium for the year 1990. The municipality of
residence for all cases and controls was identified from the death
certificate and was assumed to be the source of the subject's calcium
and magnesium exposure through drinking water. The levels of calcium
and magnesium of that municipality were used as an indicator of
exposure to those substances for an individual residing in that
municipality.
In the analysis, the subjects were divided into tertiles
according to the levels of calcium and magnesium in their drinking
water. Conditional logistic regression was used to estimate the
relative risk in relation to the calcium and magnesium levels in
drinking water. We calculated odds ratio and their 95% confidence
intervals (CIs) using the group with the lowest exposure as the
reference group.20 Coefficients with values of
P<.05 were considered statistically significant.
Table 2
The odds ratios in relation to magnesium levels in drinking water are
shown in Table 3
Migration from a municipality of high calcium and magnesium exposure to
one of low calcium and magnesium exposure or vice versa could have
introduced misclassification bias and bias in the odds ratio
estimate.22 23 The individuals included in the
present study were subjects whose residence and place of death were
in the same municipality. In the event of a death in Taiwan, there is a
social custom that the decedent's family always considers the death to
occur in the municipality where he was born. Therefore, the decedent's
residence, place of birth, and place of death are likely to be listed
as the same municipality, although the place of birth information was
not available for this data set. We believe that this ameliorates the
migration problem. In addition, all the subjects used for the
present study were at least 50 years old, and it is assumed that
the elderly are more likely to remain in the same residence and
therefore that most of their life was spent at the address listed on
the death certificate.
Dietary calcium is the main source of calcium intake. Epidemiological
studies have shown that dietary calcium is inversely associated with
blood pressure.24 25 26 27 28 With much of the
epidemiological literature suggesting a relationship between dietary
calcium and blood pressure, it would seem reasonable to expect that
intake of dietary calcium could reduce the risk of
cardiovascular events, such as stroke, that are
commonly associated with hypertension. In Taiwan, the mean daily intake
of dietary calcium is 507 mg. This figure is only 81.9% of the
recommended daily intake.29 The mean calcium
concentration in Taiwan's drinking water is 34.7 mg/L. This figure
would contribute, on average, 13.7% to an individual's total dietary
calcium intake, given a daily consumption of 2 L of water. One may
hypothesize that waterborne calcium can make an important contribution
to the total daily intake for subjects with insufficient calcium
intake. However, controlling for magnesium levels eliminates the
perceived effect of calcium levels on cerebrovascular mortality. The
reason for not finding a protective effect of calcium on risk of
cerebrovascular death may be because calcium and magnesium in the
drinking water are highly correlated (correlation coefficient, .65).
This may create collinearity in the regression model, making it
difficult to detect the effect of calcium.
In the general population, the major proportion of magnesium intake is
through food, and a smaller proportion is through drinking water (in
Sweden, generally <5% is from drinking
water).10 There are no available data for
assessing the percentage that drinking water contributes to the total
magnesium intake in the present study. Nonetheless, in the modern
world intake of dietary magnesium is often lower than the recommended
dietary amounts of 6 mg/kg per day.30 For
individuals with borderline magnesium deficiency, waterborne magnesium
can make an important contribution to their total intake. In addition,
the loss of magnesium from food is lower when the food is cooked in
magnesium-rich water.31 Magnesium in water can
also play a critical role because of its higher bioavailability.
Magnesium in water appears as hydrated ions, which are more easily
absorbed than magnesium in food.30 32 The
contribution of water magnesium among persons who drink water with high
magnesium levels could thus be crucial in the prevention of magnesium
deficiency.
The significant association between mortality from cerebrovascular
disease and the levels of magnesium in drinking water is supported by
knowledge of the functions of magnesium. Magnesium is an enzyme
(Na/K-ATPase) activator and regulates cellular energy
metabolism, vascular tone, and cell membrane ion transport.
A lack of magnesium leads to a decrease in the concentration of
intracellular potassium and an increase in calcium
levels.33 Magnesium deficiency may increase the
contractility of blood vessels, as shown in animal
experiments.34 Magnesium causes vasodilation by
stimulation of endothelial prostacyclin
release35 and, in vivo, prevents vasoconstriction
of the intracranial vessels after experimental subarachnoid
hemorrhage.36
Smoking habits and hypertension represent possibly important
confounders in the present study. There is unfortunately no
information available on these variables for individual study
subjects, and they could not be adjusted for directly in the
analysis. However, there is no reason to believe that there
would be any correlation between these confounders and the levels of
magnesium of the water. It is also unlikely that there would be a
direct relationship between other risk factors and the level of
magnesium in drinking water. In addition, fear of cerebrovascular
disease should not deter anyone from drinking water with low magnesium
levels.
In conclusion, the results of the present study show that there is
a significant protective effect of magnesium intake from drinking water
on the risk of cerebrovascular disease. This is an important finding
for the Taiwan water industry and human health risk assessment. Future
studies should increase the precision of the estimation of the
individual's intake of calcium and magnesium, through both food and
water, and control for confounding factors, especially personal risk
factors such as smoking and hypertension.
Received September 2, 1997;
revision received November 4, 1997;
accepted November 4, 1997.
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© 1998 American Heart Association, Inc.
Original Contributions
Calcium and Magnesium in Drinking Water and Risk of Death From Cerebrovascular Disease
Abstract
Top
Abstract
Introduction
Methods
Results
Discussion
References
Background and Purpose—Many studies
have demonstrated a negative association between mortality from
cardiovascular or cerebrovascular diseases and water
hardness. This report examines whether calcium and magnesium in
drinking water are protective against cerebrovascular disease.
Key Words: calcium • cerebrovascular disorders • magnesium • mortality
Introduction
Top
Abstract
Introduction
Methods
Results
Discussion
References
The relationship
between water hardness and mortality from
cardiovascular disease has been studied for more than
40 years. The association was first described in
Japan,1 where a significant correlation between
drinking water quality and mortality from cerebrovascular disease was
found. Subsequently, a number of studies conducted in various countries
have demonstrated a negative association between
cardiovascular disease mortality and water
hardness.2 3 4 5 6 7 8 9 10 11
Methods
Top
Abstract
Introduction
Methods
Results
Discussion
References
Taiwan is divided into 361 administrative districts, which will
be referred to in this report as municipalities. They are the units
that will be subjected to statistical analysis. Excluded from
the analysis were 30 aboriginal townships and 9 islets that had
different lifestyles and living environments. This elimination of
unsuitable municipalities left 322 municipalities for the
analysis.
Results
Top
Abstract
Introduction
Methods
Results
Discussion
References
A total of 17 133 cerebrovascular disease cases with complete
records were collected for the period 1989 to 1993. Of the 17 133
cases, 10 625 were men and 6508 were women. The mean calcium
concentration in the drinking water of the cases (n=17 133) was 34.5
mg/L (SD=19.5). Controls (n=17 133) had a mean calcium exposure of
34.8 mg/L (SD=19.5). The mean magnesium concentration in the drinking
water was 11.3 mg/L (SD=7.5) for the cases and 11.4 mg/L (SD=7.5) for
the controls. Both cases and controls had a mean age of 61.9 years.
Both cases and controls lived in municipalities in which 90.2% of the
population were served by a waterworks. Cases had a similar rate
(37.8%) of living in metropolitan municipalities compared with the
controls (38.3%) (Table 1
).
View this table:
[in a new window]
Table 1. Characteristics of the Study Population shows the numbers of cases and
controls and odds ratios in relation to calcium levels in their
drinking water. The crude odds ratios were significantly lower than 1.0
for the group with the highest calcium level (0.94; 95% CI, 0.89 to
0.99), but when adjusted for magnesium levels there was no difference
between the groups with different levels of calcium.
View this table:
[in a new window]
Table 2. Odds Ratios and 95% Confidence Intervals for
Cerebrovascular Death by Calcium Levels in Drinking Water, 1989–1993 . The odds ratios for
death from cerebrovascular diseases were significantly lower for the
two groups with high levels of magnesium in their drinking water.
Adjustments for possible confounders only slightly altered the odds
ratios. The adjusted odds ratios (95% CI) were 0.75 (0.65 to 0.85) for
the group with water magnesium levels between 7.4 and 13.4 mg/L and
0.60 (0.52 to 0.70) for the group with magnesium levels of 13.5 mg/L or
more.
View this table:
[in a new window]
Table 3. Odds Ratios and 95% Confidence Intervals for
Cerebrovascular Death by Magnesium Levels in Drinking Water, 1989–1993
Discussion
Top
Abstract
Introduction
Methods
Results
Discussion
References
This study uses a death certificate–based case-control study and
a drinking water quality ecology study to examine the relationship
between cerebrovascular mortality and calcium and magnesium exposure
from drinking water in Taiwan. The results of the present study
show that there is significant protective effect of magnesium intake
from drinking water on the risk of cerebrovascular disease. Despite
their inherent limitations,21 studies on the
ecological correlation between mortality and environmental exposures
have been used widely to generate or discredit epidemiological
hypotheses. The completeness and accuracy of a death registration
system should be evaluated before any conclusion based on the mortality
analysis is made. Since it is mandatory to register death
certificates at local household registration offices and since the
household registration information is verified annually through a
door-to-door survey, the death registration in Taiwan is very complete.
Although causes of death may be misdiagnosed and/or misclassified, the
problem has been minimized through the improvement in the verification
and classification of causes of death in Taiwan since 1972.
Furthermore, Taiwan is a small island with a convenient communication
network, and the accessibility of medical service facilities is
comparable among study municipalities. Mortality data differences
between the municipalities in this study do not appear to result from
systematic differences in recording and codification.
Acknowledgments
This study was supported in part by a grant from the National
Science Council, Executive Yuan, Taiwan (NSC-86–2314-B-037–089).
References
Top
Abstract
Introduction
Methods
Results
Discussion
References
1.
Kobayashi J. Geographical relationship between
chemical nature of river water and death rate from apoplexy.
Berichte d Ohara Inst of landwirtsch
Biologie. 1957;11:12–21.
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