Report of the Safe Drinking Water Committee
National Academy of Sciences

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Pages 440 through 447 of the Report of the Safe Drinking Water Committee of the National Academy of Sciences, 1977, "Drinking Water and Health," by the National Academy of Sciences, 1977. International Standard Book No. 0-309-02619-9. It is available from:

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The EPA funded the study, which states that the rates of cardiovascular death among populations drinking very soft water may be "as much as 15-20% higher than among populations using hard water", as indicated by "more than 50 studies in nine countries".

"In the United States, cardiovascular diseases account for more than one-half of the approximate 2 million deaths occurring each year... It is estimated that optimal conditioning of drinking water could reduce this cardiovascular disease mortality rate by as much as 15% in the United States "

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. . . and the problem has been the subject of several comprehensive reviews. The Subcommittee on Morbidity and Mortality, in preparing this report, has relied heavily on several of these reviews, notably those by Craun and McCabe (1975), Heyden (1976), Neri et al. (1974), Sauer (1974), Sharrett and Feinleib (1975), Schroeder and Kraemer (1974), and Winton and McCabe (1970). These reviews have been abstracted and summarized rather than reprinting the same material or attempting another review.

It should be noted, also, that the World Health Organization and the International Atomic Energy Agency consider that there is sufficient evidence for the involvement of trace elements in the pathogenesis of cardiovascular diseases to warrant international collaborative studies on the problem (IAEA, 1973; WHO, 1973). The possible causal association between water hardness and cardiovascular disease has been recognized in Great Britain to be of enough potential public health importance to have resulted in official governmental expert review of the problem (MRC, 1970; COMA, 1974).

More than 50 studies in nine countries have been carried out on possible relationship of water hardness and health. Most of the investigations were in the United Kingdom, United States, and Canada; they reveal a consistent trend of significant statistical associations between the hardness characteristics of drinking water and the incidence of cardiovascular problems (heart disease, hypertension, and stroke) and, to a lesser extent, other diseases. Generally, reports have shown an inverse correlation between the incidence of cardiovascular disease and the amount of hardness of drinking water, or, conversely, a positive correlation with the degree of softness. Studies in the United States and Canada have shown that age-adjusted cardiovascular mortality rates among populations using very soft water may be as much as 15-20% higher than among populations using hard water. The differential reported for the United Kingdom may be as high as 40%.

Cardiovascular diseases are the leading cause of death in the United States, where they account for more than 50% of all causes of death, or roughly 1 million deaths each year, and death rates from coronary heart disease have been steadily increasing over the past few decades.

It is evident, therefore, that if water factors are ultimately proven to be involved causally in the pathogenesis of cardiovascular disease, then we are confronted with a major public health problem and current water treatment practices will have to be greatly modified.

The credibility of these water-factor studies depend more on the consistent trend of the findings than their biological plausibility or the size of the correlation coefficients or the actual significance levels.

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However, there is some scientific justification for the biological plausibility of these associations. There has been increasing evidence that certain trace elements play an important role in a number of biological processes through their action as activators or inhibitors of enzymatic reactions, by competing with other elements and proteins for binding sites, by influencing the permeability of cell membranes, or through other mechanisms. It is assumed that these elements can also directly or indirectly exert an action on cardiac cells, the blood vessel walls, on blood pressure, or other systems related to cardiovascular function, such as lipid and carbohydrate metabolism. It is assumed further that water quality can affect man's trace element or mineral balance and, consequently, cardiovascular function.

As previously noted, the preponderance of reported evidence indicates statistically significant correlations between some drinking water factor(s) and the incidence of cardiovascular diseases resulting in a general impression that inorganic substances in water may be causally implicated. It must be emphasized, however, that there is considerable disagreement among various investigators concerning the magnitude or even the existence of a "water factor" risk, the identity of the water factor(s), the mode of action, and the specific pathologic effects.

Theories on Risk Factors

Several hypotheses have been offered on how components of drinking water may affect cardiovascular function and disease; these generally fall into one of the following classes:

1. That one or more of the principal "bulk" constituents of hardness in tap water are protective.

2. That one or more of the trace elements that tend to be present in hard water are protective.

3. That harmful metals are present in soft water, possibly having been picked up by leaching from the distribution system.

4. That other factors are involved. Each class of hypotheses is briefly reviewed below.

PROTECTIVE EFFECT FROM BULK CONSTITUENTS OF HARD WATER

Hardness is not a specific constituent of water, but is a complex and variable mixture of cations and anions. Several investigators have attributed the disease-protective effect of hard water to the presence of

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calcium and magnesium, which are the principal cations found in hard water. Calcium, magnesium, and hardness generally correlate well with one another. In a few studies, however, it was possible to discriminate between the two elements and treat them as separate variables. When calcium and magnesium are separately correlated with cardiovascular disease rates, calcium appears to correlate with greater significance in the United Kingdom, whereas in the United States the correlations are about equally strong for calcium and magnesium.

There is a limited amount of evidence to explain the possible mechanism whereby calcium and/or magnesium may play a role in protection against cardiovascular diseases. Experimentally, a moderate increase of calcium in the diet results in lower levels of circulating and organ cholesterol; this is speculated as a possible factor in the association noted between water hardness and cardiovascular diseases. Magnesium is theorized to protect against lipid deposits in arteries and also may have some anticoagulant properties that could protect against cardiovascular diseases by inhibiting blood clot formation. Also, there is evidence to indicate that there may be higher concentrations of calcium and magnesium in certain tissues among residents of hard water areas as compared to soft water areas.

PROTECTIVE ACTION OF TRACE ELEMENTS IN HARD WATER

There is a paucity of systematic data concerning the concentrations of trace elements as a correlate of hardness of water and cardiovascular disease rates. From a limited number of studies that have been carried out, if hard water contains protective beneficial elements (other than calcium and magnesium), vanadium, lithium, and possibly manganese and chromium emerge as candidates.

Lithium and vanadium have been reported to be negatively correlated with cardiovascular mortality. These negative correlations appear to persist and remain significant even after controlling for calcium and magnesium. The biological functions of these metals are obscure. It is speculated that lithium may have a specific influence on catecholamines and coronary-prone behavioral patterns. Vanadium is reported as an essential trace element in human nutrition and thought to inhibit hepatic cholesterol synthesis and reduce serum cholesterol. Increased intake of vanadium is believed therefore to reduce serum cholesterol. 'The mechanism is thought to be an inhibition of cholesterol synthesis, especially in young subjects.

A case is made that chromium, which is positively correlated with the

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hardness of tap water in North America (but not in the United Kingdom), may be causally involved. Experimentally, chromium deficiency produces elevated serum glucose and cholesterol levels and increased deposition of aortic plaques. Though quantitative estimates of daily chromium requirements cannot be given yet, it is thought that the chromium level in hard water may help protect against a deficiency. Similarly, it is speculated that hard water may protect against a deficiency of manganese which also experimentally is associated with decreased glucose tolerance.

HARMFUL ELEMENTS IN SOFT WATER

Soft water tends to be more corrosive than hard water. As a result certain trace metals are found in higher concentrations in soft than in hard water. Several such metals have been suggested as possible intermediaries in the increased cardiovascular disease rates associated with soft water. Based on very limited data, cadmium, lead, copper, and zinc have been suspected to be possibly involved in the induction of cardiovascular disease. These metals often occur in plumbing materials and have been found to leach into soft drinking water.

There is evidence that relatively low doses of cadmium can produce hypertension in rats. It is known that the metal can accumulate in human kidneys and produce renal damage and presumably could affect blood pressure. However, direct evidence linking cadmium in water to heart disease in humans is lacking.

Several studies have shown elevated levels of blood lead occurring among persons living in homes having lead plumbing and soft water, or both. But the relationship between these elevated blood lead levels and cardiovascular disease remains unclear.

There are limited data suggesting that the intake levels of copper and zinc from soft water may adversely affect cardiovascular disease rates. However, there are conflicting data from other studies. Still other studies suggest that the discrepancies may be due to the failure to examine critically the ionic form and the intake ratios of the suspect metals from all sources, particularly the Zn:Cu and the Cd:Zn ratios as well as various other metabolic variables.

OTHER FACTORS AND CONFOUNDING VARIABLES

From the above discussion, it is apparent that there is no shortage of hypotheses to explain how components of drinking water might affect

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cardiovascular function and disease. It is necessary to consider these hypotheses along with other factors and some confounding variables.

Several cations found predominantly in hard water are theorized to exert a beneficial effect on cardiovascular function, and other cations found in soft water, to exert a detrimental effect. The question often raised is whether drinking water can provide enough of these elements to have any significant impact on the pathogenesis of cardiovascular diseases when considered in the context of the total intake of these elements through other dietary and environmental pathways. Hard or mineralized water generally would supply less than 10-15% of the total dietary intake for calcium and magnesium.

Water provides even a smaller proportion of the total intake for the various suspect trace metals with the possible exception of lead. The largest proportion of trace metal intake from water compared to food is for zinc, but even for this water provides only about 4% of its total dietary intake. For all other suspect metals drinking water provides under 4% of total intake. The concentrations of lead in certain drinking waters may exceed 100 µg/liter as compared to an average adult daily dietary intake of about 300 µg.

Several investigators, however, point out that the amount of these elements provided through drinking water relative to other sources is less important than their chemical form. It is theorized that trace elements often occur in a chelated form in foods and may be less available metabolically than the ionized form that generally occurs in water. Also, the valence form of elements found in water may differ from that in foods and affect metabolic behavior.

Another possible variable is the different effect of hard and soft waters on the mineral composition of foods during cooking. It is theorized that soft water may remove a significantly higher proportion of various "protective" nutrients and elements from foods during cooking than do hard waters.

Most of the studies carried out to date correlate mortality rates with measurements made on raw rather than on finished water; the correlations were of lesser statistical significance when finished water was used.

There was considerable variation in the study design and methods among the numerous investigations reported. As previously noted, most of the studies report a statistically significant correlation between water hardness and one or more of several cardiovascular diseases. It is not possible, however, to quantitatively compare the data from many of these studies because of the different criteria and indices used in the specification of cause of death. The case for a causal association of water factors to any specific pathologic effects is thought to be further

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weakened by several reports of correlations of the water factor with other causes of death, such as bronchitis, infant mortality, malignancies, cirrhosis, and other noncardiovascular causes of death. Despite the consistent trend for most of the reported studies, a few studies have shown negative or conflicting results for different age and sex groups. For example, in Holland and Sweden, hard water was correlated with decreased cardiovascular mortality among women but not men, and an opposite finding emerged from a study in Newfoundland.

The strength and specificity of the correlative studies have varied depending on the sample sizes of the area and population. In general, the relationship appears stronger in larger and more populous areas.

To some extent these differences are probably due to a lack of sensitivity of correlation coefficients related statistically to the size of the sampling unit. Obviously, smaller geographical units with smaller populations would tend to have less stable death rates and consistency than larger ones, so that any variable will tend to correlate less well with smaller geographical and population bases. But it should be noted that the size of the metropolitan area and population density tend to correlate well with cardiovascular disease rates independently of water quality. This is attributed to various cultural and socioeconomic factors that appear to influence cardiovascular disease mortality rates. On the other hand, less urban areas are more likely to-use relatively hard groundwater and, conversely, larger metropolitan areas are usually more dependent on softer surface waters. In a few studies where corrections for socioeconomic factors were attempted, the correlations with hardness of water still exist but with a reduced statistical significance. It is possibility that both urbanization and water mineralization have an effect on cardiovascular disease rates and could be interacting or acting separately.

Several studies have shown statistically significant correlations of death rates with various geographical and climatic variables, especially rainfall, independently of water-quality variables. Much more work must be done on the possible associations and interrelationships of variables such as rain, soil chemistry, and human nutrition with water-quality and cardiovascular disease rates.

From this review, it is clear that there is no shortage of hypotheses related to how the components of drinking water might affect cardiovascular function and disease. Despite the large body of evidence supporting the hypotheses, there are too many confounding variables and discrepancies in the data to permit any scientifically sound conclusions as to the specific role of water factors in the pathogenesis of cardiovascular diseases.

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Summary-Water Hardness and Health

There is a large body of scientific information that indicates certain inorganic or mineral constituents of drinking water are correlated with increased morbidity and mortality rates. These constituents by usual definition are not considered to be "contaminants," as they often are associated with the level of "hardness" of drinking water and occur naturally or are picked up from water-treatment or distribution systems. Hardness is due primarily to the presence of ions of calcium and magnesium and is expressed as the equivalent quantity of calcium carbonate (CaCO3). Water with less than 75 mg CaCO3/liter is generally considered soft, and above 75 mg/liter as hard.

A voluminous body of literature suggests that in the United States and other developed nations, the incidence of many chronic diseases, but particularly cardiovascular diseases (heart disease, hypertension, and stroke), is associated with various water characteristics related to hardness. Most of these reports indicate an inverse correlation between the incidence of cardiovascular disease and the amount of hardness. A few reports also indicate a similar inverse correlation between the hardness of-water and the causes of risk from several noncardiovascular causes of death as well.

Several hypotheses are reported on how water factor(s) may effect health; these mostly involve either a protective action attributed to some elements found in hard water or harmful effects attributed to certain metals often found in soft water.

The theorized protective agents include calcium, magnesium, vanadium, lithium, chromium, and manganese. The suspect harmful agents include the metals cadmium, lead, copper, and zinc, all of which tend to be found in higher concentrations in soft water as a result of the relative corrosiveness of soft water.

It is evident from the review of the literature that there is considerable disagreement concerning the magnitude or even the existence of a "water factor" risk, the identity of the specific causal factor(s), the mode of action, and the specific pathologic effects.

Nevertheless, the preponderance of reported evidence reflects a consistent trend of statistically significant inverse correlations between the hardness of water and the incidence of cardiovascular diseases. As a result, there is a general impression that harmful elements in soft water and/or protective elements in hard water are causally implicated in the pathogenesis of cardiovascular and possibly other chronic diseases.

The wide spectrum of alleged associated effects, the lack of consistency in theorized or reported etiologic factors, the very small quantities of

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suspect elements in water relative to other sources, and the discrepancies between studies raise serious questions as to whether drinking water really serves as a vehicle of causal agents, is an indicator of something broader within the environment, or represents some unexplained spurious associations. Despite these uncertainties, the body of evidence is sufficiently compelling to treat the "water story" as plausible, particularly when the number of potentially preventable deaths from cardiovascular diseases is considered. In the United States, cardiovascular diseases account for more than one-half of the approximate 2 million deaths occurring each year. On the assumption that water factor(s) are causally implicated, it is estimated that optimal conditioning of drinking water could reduce this annual cardiovascular disease mortality rate by as much as 15% in the United States.

In view of this potential health significance, it is essential to ascertain whether water factors are causally linked to the induction of cardiovascular or other diseases and, if so, to identify the specific factors that are involved. Much more definitive information is needed in order to identify what remedial water treatment actions, if any, can be considered.

REFERENCES FOR TRACE METALS

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Ackermann, W.C. 1971. Minor Elements in Illinois Surface Waters. Illinois State Water Survey Technical Letter 14.

Adamson, A.H., DA. Valks, M.A. Appleton, and W.B. Shaw. 1969. Copper toxicity in housed lambs. Vet. Rec. 85:368-369.

Aikawa, J.K., E.L. Rhoades, and G.S. Gordon. 1952. Urinary and fecal excretion of orally administered Me. Proc. Soc. Exp. Biol. Mod. 98:39-3 1.

Albert, R.E., R.E. Shore, A.J. Sayers, C. Strehlow, T.J. Kneip, B.S. Pasternack, AJ. Friedhoff, F. Covan, and J.A. Cimino. 1974. Follow-up of children overexposed to lead. Environ. Health Perspect., Exp. Issue no. 7, pp. 33-39.

Alberts, J.J., J.E. Schindler, and R.W. Miller. 1974. Mercury determinations in natural waters by persulfate oxidation. Anal. Chem. 46:434-437.

Aldous, K.M., D.G. Mitchell, and K.W. Jackson. 1975. Simultaneous determination of seven trace metals in potable water using a Vidicon atomic absorption spectrometer. Anal. Chem. 47:1034-1037.

Alexander, F.W., H.T. Delves, and B. E. Clayton. 1973. The uptake and excretion by children of lead and other contaminants. In Environmental Health Aspects of Lead, Proc. Int. Symp., Amsterdam, Oct. 2-6,1972. Luxembourg, Commission of the European Communities, pp. 319-331.

American Public Health Association. 1976. Standard Methods for the Examination of Water and Wastewater, 13th ed. Washington, D.C.,

American Society for Testing and Materials. 1970. Annual Book of ASTM Standards, pt. 23, Water and atmospheric analysis. Philadelphia .