Salt taste and hypertension: A critical review of the literature

J Chron Dis Vol. 37. No. 3. pp. 195-208. 1984 Prmted

in Great

Britain.

SALT

All rights reserved

Copynght

0021-9681/84 $3.00 + 0.00 ‘c‘ 1984 Pergamon Press Ltd

TASTE AND HYPERTENSION: A CRITICAL REVIEW OF THE LITERATURE RICHARD D. MATTES Monell Chemical Senses Center, Philadelphia, PA 19104. U.S.A (Received in revised .fbrrn 13 July 1983)

Abstract-Studies of the salt taste sensitivity, responsiveness, preference, and appetite of normotensive and hypertensive individuals have yielded therapeutic, diagnostic, predictive, and mechanistic findings related to hypertension. Following a brief description of the nature of these taste parameters, findings pertaining to the association between each and hypertension are critically reviewed. Potential clinical implications of this information, as well as the need to exercise caution in the translation of taste data into dietary practice are also discussed.

INTRODUCTION

of taste has been implicated in the causation or manifestations of various pathologies, such as hypertension [l-4], cancer [5-71, diabetes [8,9], and dental caries [lo, 1I]. The impetus to investigate the relationship between salt taste and hypertension stems from the prevalence [12] and high costs [13] of this disorder as well as the widely-recognized (though poorly understood) association between salt intake and blood pressure. As numerous comprehensive reviews of this latter issue are available [e.g. 14-181, the present review will focus on studies of salt taste function in normotensive and hypertensive humans. The relationship between salt taste and hypertension has also been reviewed [19,20]. In 1978, Contreras [19] evaluated the existing data related to the salt taste sensitivity of hypertensives and normotensives, though this publication focuses on animal literature. Simpson [20] considered the evidence concerning salt taste sensitivity and preferences. The present review was prompted by new human data on a variety of measures of taste function (i.e. sensitivity, responsiveness, preference, and appetite), differences in the interpretation of the older findings, and the need to alert nutritionists and clinicians to inappropriate interpretations and applications of taste data. The taste parameters listed above will be characterized, followed by an explanation of the relevant salt taste-hypertension findings. The potential clinical implications of these data are also considered.

THE

SENSE

SENSITIVITY

Sensitivity may be defined as the ability to detect or recognize gustatory stimuli. Detection and recognition thresholds are extensively used measures of this taste attribute. The former threshold is defined as the minimum physical intensity of a stimulus that a subject can detect. The minimum physical intensity of a stimulus that a subject is capable

All correspondence should be addressed to: Dr Richard Mattes, Monell Street, Philadelphia, PA 19104, U.S.A. This research was supported by funds from the National Institutes 2-T32-NS07 176.04. 195

Chemical of Health

Senses Center, Research

3500 Market

Training

Grant

196

RICHARD D. MATTES

of identifying as a given quality (e.g. salty for a saline solution) is termed the recognition threshold. All thresholds, however, are a form of discrimination relative to a background medium. Thus, the conditions under which a threshold is determined can greatly influence the resulting value. In addition, the sensitivity of an individual varies due to the influence of numerous endogenous and exogenous variables. With respect to the salty taste, one of the most important of these factors is the salivary sodium concentration. The taste receptors are bathed in saliva, and adapt to the sodium level of this fluid. To elicit a salty sensation, this level must be exceeded by a given amount in an individual. Attempts to assess salt sensitivity can yield different results depending on the level of adaptation of the taste receptors [2 1,221. NaCl taste sensitivity

and hypertension

Sensitivity has been the most extensively studied taste parameter with respect to hypertension. Fallis et al. [I] were the first group to assess the NaCl detection and recognition thresholds of normotensives and hypertensives (diastolic blood pressure (DBP) > 100 mmHg). While no differences in NaCl detection thresholds were observed, the hypertensives displayed elevated recognition thresholds. Sensitivity for dextrose was similar in the groups, indicating that the taste discrepancy was specific for salt. These authors suggested that “. . . hypertensives may eat more salt because they cannot taste it as well as can normotensive individuals.” Furthermore, they implied diminished salt taste sensitivity may be a factor in the etiology of hypertension, These inferences are based upon the assumptions that: (1) sensitivity and intake are closely linked and (2) hypertensives actually consume more salt than normotensives. To date, however, neither of these assumptions has been substantiated. Fallis et al. suggested that a genetic basis for their findings be sought by testing the relatives of hypertensives. This was done by Bisht et al. [2] with a sample of 310 subjects. They assessed groups of normotensive controls, hypertensives (no blood pressure criteria were stated), diabetics, and individuals who had first degree relatives falling into one of these categories (referred to as “sibs”). Hypertensives, hypertensive diabetics, and hypertensive sibs had higher recognition thresholds for salt compared to normotensive controls. The authors concluded that there may be a genetic basis for the taste effect. In contrast to this view, Langford and Watson [23] suggested that environmental factors may be primary determinants of both blood pressure and salt taste sensitivity. In a sample of 113 pairs of sisters, they obtained a correlation coefficient (r = 0.445) for salt taste sensitivity which resembled that observed for sodium excretion and selected anthropometric indices. The coefficient for diastolic blood pressures was somewhat lower (r = 0.37) and similar in both half and full siblings. These observations do not, however, preclude some genetic contribution to these physiologic parameters. While several additional studies have shown elevated salt recognition thresholds among hypertensives [24,25], they are difficult to interpret due to questionable methodologies. For example, in the interim between the Fallis et al. [l] and Bisht et al. [2] investigations, Wotman et al. [24] obtained similar results. Thirty-seven of the 60 hypertensive subjects (BP > 140/90 mmHg), however, were under treatment for their disorder. Therapy included a variety of antihypertensive medications, some of which have been reported to lower salt taste thresholds [26]. While this drug action would tend to obscure the noted group differences, and is therefore not a relevant confounding factor of this study, the effects of other classes of prescribed antihypertensive medications on taste function have not been evaluated. They might shift salt thresholds in either direction. Thus, pending further study of this issue comparisons between treated hypertensives and controls are not appropriate. Another study reported that 17 hypertensives displayed elevated salt recognition thresholds compared to 23 normotensive controls [25], however, the method of stimluli presentation was not explicitly stated. It is reported only that stimuli were applied to the tongue. In previous studies, taste stimuli were sipped from a cup and expectorated. The results of this study are consistent with those reported thus far, although absolute values of the thresholds are higher than others found in the literature.

Salt Taste and Hypertension

197

Finally, relative to pre-treatment values, Langford and Watson [26] observed a decreased salt threshold (it could not be determined whether it was a detection or recognition threshold) in 54 newly diagnosed hypertensives administered diuretics for 2 weeks. Furthermore, the changes in diastolic blood pressure were significantly correlated with thresholds among individuals with a decreased threshold. No association was noted, however, among subjects whose thresholds were increased. Reports of elevated recognition thresholds among hypertensives are strengthened by two points. First, in many studies, both detection and recognition thresholds were determined. In every case, only recognition thresholds were found to vary. Thus, the apparent effect is not attributable to a generalized taste aberration. Second, it is unlikely that the results are due to adaptation effects. Untreated hypertensives present lower salivary sodium levels than normotensive controls [27], and could be expected to display lower recognition thresholds. A recent study, however, failed to find differences in salivary sodium concentrations between 10 essential hypertensive patients and 10 normotensive controls

WI. Two investigations failed to detect salt sensitivity differences between normotensive and hypertensive subjects. Henkin [29] found that the degree of aldosterone hypersecretion in 50 patients with hypertension (DBP > 100 mmHg) and 10 with primary hyperaldosteronism did not influence salt taste acuity, nor did the degree of dietary sodium restriction or overall blood pressure status. Schechter et al. [3] observed no significant differences in detection or recognition thresholds among a group of 16 hypertensive (DBP > 100 mmHg) and 26 normotensive subjects. In contrast to the investigations reporting positive findings, these studies employed a forced-choice three-stimulus drop technique, which may account for the discrepant findings. The sip and spit procedure is believed to be more sensitive than the three-stimulus drop technique [30]. A final negative result involved 95 children, 1l-16 years of age [31]. They represented the low, middle, and high blood pressure percentiles of a group of 4800 Muscatine Iowa school children. No relationship between blood pressure and detection thresholds was observed using the three-stimulus drop technique. However, few of the children actually had markedly elevated blood pressure levels. The negative findings of this study are consistent with all previous reports with respect to detection thresholds. Recognition thresholds were not determined. In summary, studies on salt taste sensitivity indicate that while detection thresholds seem stable between normotensives and hypertensives, recognition thresholds may be elevated in persons with this disorder. The few studies failing to observe an elevation in salt recognition thresholds employed a similar taste testing procedure which is believed to be less sensitive than the methods employed in the investigations noting meaningful salt sensitivity shifts. RESPONSIVENESS

There is no widely accepted term to describe an individual’s ability to discriminate between and assess the intensity of stimuli above threshold levels i.e. suprathreshold concentrations. The term “responsiveness” will be adopted for this purpose. There are numerous methods available for evaluating responsiveness (e.g. magnitude estimation [32-341, ranking [35], rating scales [35]) which are commonly referred to as “scaling” procedures. Such procedures require subjects to assign a label or value to a stimulus or generate a physical response in proportion to a given scale or comparison stimulus. Two scaling procedures have been employed in the study of taste and hypertension, magnitude estimation and line scale ratings. The motivation to measure suprathreshold perception is based primarily upon two points. First, threshold sensitivity does not necessarily correlate with suprathreshold perception measured via scaling procedures [36]. When the taste receptors are adapted to elevated sodium levels, thresholds can be elevated (depressed sensitivity) while suprathreshold perception is normal [34]. Conversely, persons recovering from head and neck radiation therapy may regain normal threshold sensitivity

198

RICHARD D. MATTES

relatively quickly while their suprathreshold function remains depressed for some time [34]. Therefore, assessment of thresholds and responsiveness provides complimentary data covering a wider range of the taste sense than either alone. The observation that normotensives and hypertensives present similar detection thresholds, but discrepant recognition thresholds, indicates that the alteration in taste is not uniform across concentrations. Thus, assessment of a larger segment of this range by a scaling technique seems warranted. The second advantage of suprathreshold testing lies in the fact that evaluations in this range of the taste sense more closely resemble those made when consuming “normal” diets and, as a consequence, may be more closely related to preferences and actual intake [36]. This last point, however, requires further verification. NaCl taste responsiveness and hypertension Bernard et al. [37] examined salt taste responsiveness in seven hypertensives and seven controls with a magnitude estimation procedure. The mean blood pressure of the hypertensive subjects was 142/98 mmHg and they were all considered to have low plasma renin activities. The decision to focus attention on low renin hypertensives was based upon an hypothesis that such individuals possess an increased blood volume and could therefore be expected to display high salt intakes. While this classification system is questionable [38,39], the isolation of more homogenous groups of hypertensives for study holds merit since hypertension appears to be a disorder with multiple etiologies [40]. Subjects tasted a standard sample and compared a series of stimuli to the standard. Such a procedure can lead to greater variability of responses than if the standard is presented before each stimlulus [35]. This fact and the small sample size renders inconclusive this investigation’s finding of no group differences in salt taste responsiveness. The other available study on this topic [41]*, however, both confirms and extends these findings in a larger population with a more stringent testing protocol. In this study, three groups of individuals (normotensives, prehypertensives, hypertensives) were identified based upon the mean of four blood pressure readings, the presence of a family history of hypertension, and several additional hypertension risk factors (i.e. relative weight, heart rate, salt intake).? The 35 normotensives had mean blood pressures less than or equal to 120/80 mmHg and none of the stipulated hypertension risk factors. The criteria for the 17 hypertensives was a minimum mean blood pressure of 165/95 mmHg. Fifteen of the 17 hypertensives (88%) also had a positive family history. A third group, labeled “prehypertensives”, possessed two or more risk factors, one of which was a family history (present in all 35 individuals) or a blood pressure between 130/85 and 140/90mmHg. Subjects assessed aqueous saline solutions with a magnitude estimation technique (where the standard was tasted before each sample stimuli), and food models (tomato juice, rice) were evaluated with a line scale rating form. Neither scaling method yielded differences in responsiveness between the groups. Furthermore, the responses of prehypertensive individuals, as defined by Mattes et al. [41], were indistinguishable from those of the normotensives and hypertensives. No group showed a strong correlation between responsiveness and actual intake, though a relatively insensitive tool for assessing intake, a food frequency questionnaire, was employed. The wide scope of these two studies provides reasonable evidence that taste responsiveness is not affected by hypertension. Dissimilar testing protocols involving both *In a 1978 publication [19], mention was made of a study by Moskowitz and Abramson where the suprathreshold salt taste function of hypertensives and controls was assessed. The subjects of this investigation, however, were patients with renal dysfunction and on dialysis, but not suffering from documented hypertension (Moskowitz, personal communication). tThe advisability of assessing the presence of hypertension risk factors, such as family history, when studying correlates of this disorder has been demonstrated by several groups. Grim et al. [42] found normotensive first degree relatives of hypertensives to display higher PRA values and a diminished naturetic response to a salt load compared to normotensive controls. Pietinen et al. [43] observed an association between blood pressure and sodium and chloride excretion and Na/K ratio only in subjects with a positive family history of hypertension.

Salt Taste and Hypertension

199

aqueous NaCl solutions and food systems covering a wide range of salt concentrations yielded similar conclusions. In addition, different strictly defined subgroups of hypertensives were evaluated in an attempt to maximize the probability of observing significant taste effects. PREFERENCE

Studies of taste preferences for foods and model systems have proven difficult to execute and interpret. In addition to the actual taste of a compound or food, preferences are governed by color, texture, aroma, temperature, dietary history, genetics, physical state, psychological state, the interaction between all of these, and more [44]. Two methods for the study of preferences predominate in the literature. In one, subjects rate individual foods, groups of foods or model samples according to their attitude towards them (e.g. by using hedonic category scales or rankings). In the second method, individuals indicate how frequently they would like to consume a particular food or menu. These two measures contribute unique information. It is entirely possible for an individual to like an item a great deal, but not care to consume it regularly. Alternatively, less desired foods may be ingested frequently without complaint. Among Air Force personnel in a cafeteria setting, it was found that a “liking for the item” was the most commonly stated reason for selecting a food [45]. Variety, a measure of preferred frequency, was the third most commonly observed factor. Validation of these preference rating measures in terms of predicting intake has been difficult. Typically, testing is performed in a laboratory setting where short-term exposures to an item or menu are rated by verbal judgements. Subjects are not usually allowed to consume the item(s). This is an artificial situation and not optimal for obtaining externally valid results. The effects of early food experiences on preference and intake in later life are also important and controversial. It has been suggested that a high salt diet during infancy may increase the risk of developing hypertension in later years by establishing a heightened preference for, and intake of, salt [16,46.47]. Two assumptions underlie this theory: (1) that food attitudes and intake habits for a specific taste quality (i.e. salt) are established by early exposure to the taste, and (2) that salt intake serves as a contributing factor in the onset of hypertension. Neither assumption, however, has been substantiated in humans. Nevertheless, the American Academy of Pediatrics’ Committee on Nutrition [48] and the Subcommittee on Safety and Suitablity of MSG and Other Substances in Baby Foods [49] recommended a reduction in the sodium content of infant formulas and foods. Industry has voluntarily complied with these recommendations. While this action may prove beneficial, the single study which directly addressed this issue found no correlation between salt intake during the third to eighth month of life and salt preference at 8 years [50]. However, preference was assessed only by a questionnaire completed by each child’s mother. The salt intake (as measured by excretion of the nutrient) and blood pressure of the S-yr-olds were also unrelated to their intake of salt at 3 and 8 months of age. NuCI taste preference and hypertension Schechter et al. [3] presented subjects with two bottles, one containing water and the other a saline solution to see which would be consumed in greater quantity. Patients with essential hypertension and on a 9 mEq/d sodium diet had a preference for salt 2.5 to 2.8 times that of normotensive controls. The very low sodium intake of these subjects, and the fact that intakes remained well below national averages when subjects were offered free access to saline solutions, makes extrapolation of results to free-living Americans difficult. Using soups salted to three different levels, Paul [51] reported that hypertensive men preferred the weaker of the three samples offered. Since the preferences of the normotensives were not described, no conclusion about any shift in preference among hypertensives can be made. Lauer et al. [31] observed no correlation between blood

200

RICHARD D. MATTIB

pressure and salt preference in their sample of primarily normotensive adolescents. Subjects rated salted tomato juice and beef broth samples using a nine point hedonic category scale. Allowing subjects to salt juice and broth samples to preference also revealed no significant correlation between blood pressure and salt preference. Similar results were obtained by Pangborn and Pecore [52] in a group of normotensive university students, again using an ad iibitum salting task with tomato juice. Bernard et al. [37] assessed preferences of 22-61-yr-old subjects on a nine point hedonic scale, and by magnitude estimation. The hypertensive subjects preferred the saltier samples based upon magnitude estimation, but not when using the category scale. Bernard et al. suggested that the category scale may have forced all subjects to use the same limited set of numbers, while magnitude estimation offered them more freedom to express their perceived preferences. Thus, greater validity was accorded the magnitude estimation data. However, a line scale response form, which does not employ a predetermined set of numeric responses yielded data consistent with the Bernard et al. category scale results [41]. In addition to having subjects rate salty foods on a line scale, Mattes et al. [41] allowed their subjects to salt a low sodium tomato juice sample to preference. Subjects also indicated the acceptability of various high salt density foods via a food action rating (FACT) scale [53], composed of a series of graded action and affective-type statements describing attitudes towards a given food or beverage. The FACT scale assessed a different aspect of taste preference than the ratings for salted tastants. While the latter may provide information on preferred levels of salt in foods, the FACT scale is designed to convey how well highly salted foods are liked. Consistent with normotensive 1I-16-yr-olds [31] and 1%22-yr-olds [52], 20-60-yr-old normotensive, prehypertensive, and hypertensive subjects [41] failed to display significant differences on the ad libitum salting task. Group FACT scale ratings were also similar. None of the three measures of salt preference correlated with responsiveness ratings or actual intake. Because salt restriction is often recommended for hypertensives, assessing the salt preferences of normotensives and hypertensives on low sodium diets also merits consideration. Based upon anecdotal evidence, Dahl et al. [54] suggested that the desire to consume salt diminishes after adherence to a lowered salt diet for several months. Recently, two studies provided empirical support for this contention. In one investigation [55], 15 Caucasian males with a mean blood pressure of 133/87 mmHg, were placed on reduced sodium diets (approximately 3.89 g/day) for 5 months. Though the changes were not statistically significant, peak preference ratings for salted broth and tomato juice samples shifted from a concentration of 98.3 to 64.4mmol. In another study [56], the salt concentration of maximum pleasantness of soup and cracker samples declined significantly among eight normotensive subjects who reduced their sodium intake from a mean of 3.2 g/day to approximately 1 g/day over a 5 month period. No change was noted among five control subjects on ad libitum salt diets. In contrast to these findings, Bertino et al. [57] reported an enhanced preference for salt in three normotensive males placed on salt restricted diets (approximately 1.73 g/day) for three weeks. These authors now suggest that there may be a biphasic hedonic response to salt restricted diets. When initiating such a diet, one is still accustomed to high salt intakes and the relative diminution elicits a heightened preference for the taste. Once acclimated to the diet (perhaps l-2 months after its initiation), preferences adjust downward in accordance with the lower level of salt exposure. Assessment of the validity of this hypothesis and its clinical importance for hypertensives is hampered by the fact that very few subjects, most of whom were normotensive, have been evaluated. Additional work on this issue is needed. The weight of the evidence indicates that the salt taste preference behavior of normotensive and hypertensive individuals is similar. The only evidence contrary to this conclusion was obtained in a sample of individuals on extremely low sodium diets [3] (possibly reflecting a physiologic need state) and a small group of subjects who displayed discrepant responses on different response forms [37]. The only positive findings are based upon responses for aqueous NaCl solutions. Food systems have consistently failed to reveal significant differences between normotensives and hypertensives. Shifts in salt

Salt Taste and Hypertension

201

preference have been reported among normotensive and hypertensive subjects on salt restricted diets, but the extent and time course of such changes remains poorly characterized. The possibility that hedonic as well as other taste responses are governed by one’s exposure to a food or taste quality, independent of the influence of pathology, warrants further study. APPETITE

Salt appetite has been defined as “. . . a strong motivation to seek, obtain, and ingest sodium” [%I. Arguments have been proposed for both innate [59] and learned [14,6&62] mechanisms of specific appetites. A less recognized view holds that specific nutrients are ingested regardless of need because they are intrinsically pleasing to the organism [63,64]. Evidence that animals will seek and ingest NaCl in preference to other non-sodium salts on their first exposure to such stimuli supports the hypothesis of an innate mechanism for salt appetite. Data has been obtained from animals depleted of sodium [65,66] as well as those in sodium balance, but subjected to physiological conditions often associated with a deficiency state [67]. These conditions include, but are not limited to: a negative sodium balance, hypovolemia, enhanced peripheral activity of the renin-angiotensin-aldosterone system (RAS), and central stimulation by renin or angiotensin II [58,68-711. In need-free laboratory rats, the taste for sodium is an important factor influencing its ingestion [72] and sodium appetite is dependent on a functional gustatory sense [73-751. Furthermore, need-free rats will ingest excessive quantities of NaCl when presented with weak, especially isotonic saline solutions [72,73]. Based upon these findings, it has been suggested that higher mammals also possess an innate liking for salt [73] which may, in turn, influence its ingestion [76]. Examples of an apparently innate salt appetite have also been documented in humans [77-791, but are limited to cases involving patients with sodium wasting pathologies. Unlike the animal findings, studies involving humans in a “need-free” state generally support the learned behavior hypothesis for salt appetite. For example, studies suggest that while the salty taste is discernible at birth, it is not preferred over water [80]. Preference behavior clearly does not compare to positive responses noted for sweet stimuli during this stage of the life cycle [80]. Thus, no innate salt preference which may predispose neonates and/or infants to consume salty stimuli appears functional. Preferences among infants for salty solid foods are less easy to interpret, due to a poor understanding of the role of past food experiences and the importance of the context in which foods are presented [80]. Additional evidence supporting an acquired appetite hypothesis includes: (1) studies showing that the salt habits of geographically separate, but genetically similar populations can differ radically [8 1,821; (2) reports of isolated human societies who have been found not to use salt [e.g. 63,81, 83-861 and who, upon their initial exposure to the substance, deem it distasteful [63,81]; and (3) findings in normotensive [56] and hypertensive [55] subjects that the desire to consume salt diminishes over time when intake of the nutrient is limited. That Americans typically ingest excessive quantities of salt (relative to physiologic need), may or may not be viewed as salt appetite behavior. When presented with a large and diverse array of food items containing various levels of sodium (as is the case in American grocery stores and markets) diets are freely selected which contain high levels of the nutrient. This behavior, however, is not as striking as the powerful directed drive to consume salt by individuals suffering from certain pathologies, such as Addison’s Disease [77-791. The latter example is clearly a case of a salt appetite while characterization of the former is dependent upon the definition of the taste parameter adopted. A liberal interpretation would view typical American consumption habits as a manifestation of a salt appetite while a more strict view would not. A better understanding of salt appetite behavior in humans is needed. Development of the most appropriate and effective measures to curb current consumption levels, as has been recommended [X7,88], may be dependent upon this knowledge. Benefit should also

202

RICHARD D. MATTES

be realized by individuals treated for pathologies sodium balance.

involving a marked negative shift in

NaCl appetite and hypertension Within a population, hypertensives and normotensives seem to consume similar quantities of salt [89-941. Thus, hypertensives exhibit salt appetite behavior to the same extent as individuals with normal blood pressure. A stronger drive to consume the nutrient has not been reported. This situation is actually not surprising since the physiologic conditions commonly associated with the behavior (mentioned earlier) are not consistently present among hypertensives. Sodium appetite may be expressed during treatment with diuretics as shown by both animal [69,95] and human [9698] studies. Human hypertensives placed on such therapy increased their intake of sodium, as evidenced by elevated urinary excretion of the nutrient. For example, Parijs et al. [96] evaluated 17 hypertensive patients under four conditions: (a) regular diet and placebo, (b) regular diet and diuretic (c) salt restricted diet and placebo and (d) salt restricted diet and diuretic. Urinary Na excretion values were higher among patients taking diuretics relative to values obtained for placebo trials, Rock and Hall [98] noted a similar effect in 66 black hypertensives placed on a thiazide diuretic without dietary counseling and Langford et al. [97] reported 27 black woman undergoing antihypertensive therapy, usually involving a thiazide diuretic, excreted higher levels of Na than non-treated patients. While the independent replication of this observation by three groups strengthens the confidence that can be placed in the effect, it is important to recognize several methodological issues which hamper the interpretation of these findings. First, the duration of diuretic use varied across studies and in no case was it documented that subjects were in a steady state condition with respect to sodium balance. Second, all observations are based upon single 24-hr urinary collections. The validity of urinary Na excretion values obtained under such conditions has been questioned as an indicator of sodium intake [99-1021. Bing et al. [103] did not observe a salt appetite enhancing effect of thiazide diuretics in a group of 36 British patients studied over a 2 year period although seven subjects did show marked elevations of urinary Na excretion. The generally negative findings of this study may be attributable to a difference in the patient population evaluated. In the investigations reporting an enhanced salt intake among treated patients, mean diastolic blood pressures exceeded 100 mmHg. Bing et al. [ 1031did not report blood pressure levels, but patients were described as having “mild hypertension”. Langford et al. [97] noted that the salt appetite stimulating effect of diuretics was most pronounced among patients with diastolic blood pressures greater than 100 mmHg. A recent study on hypertensive patients who discontinued diuretic treatment after a 5 year course of such therapy also failed to note a diuretic-induced enhancement of salt appetite [104]. Eighty-two patients were divided into three groups; (i) controls who continued to take a diuretic, (ii) patients who discontinued their use of a diuretic, but who were provided dietary counseling on low sodium diets and (iii) patients who stopped using a diuretic and received no dietary guidance. No group differences were observed in either baseline urinary Na excretion levels or values obtained 4 months after the initiation of treatment modifications. Plasma renin levels were more markedly reduced among patients who were withdrawn from the diuretic, suggesting there was a change in the sodium balance among these individuals. The failure to note changes in urinary Na excretion in these patients relative to drug-using controls indicates that the mild negative sodium balance induced by diuretics did not elicit a shift in salt appetite. No explanation for the negative observations of this latter study is apparent although it is possible that there is only a transient shift in salt appetite among diuretic users. Parijs et al. [96] evaluated patients following a 4 week course of diuretic treatment and Rock and Hall [98] tested hypertensives after 6 months of therapy. The duration of diuretic use among patients studied by Langford et al. [97] was not stated. In contrast, the subjects participating in the investigation of Levine and Chan [IO41 had been on medication for

Salt Taste and Hypertension

703

5 years and may have re-adjusted their salt intake back to pretreatment levels. Thus, withdrawal of the diuretic from such patients would not reveal shifts in Na intake. A prospective study of diuretic users is needed to address this hypothesis. In summary, there is no evidence that untreated hypertensives possess a heightened salt appetite relative to normotensives. The potential of diuretic treatment to induce salt appetite, however, warrants further consideration since such an effect might compromise the efficacy of treatment on two levels. First, if individuals prescribed these drugs unwittingly increase their salt intake, they will be replensishing the body with the ion the diuretic treatment was designed to eliminate. Thus, plasma volume and, as a consequence, blood pressure will not be decreased to the level expected. Data supporting this concern has been reported [69,95, 105-1071. Second, the diminished efficacy of the diuretic may necessitate the addition of other antihypertensive medications (e.g. /?-adrenergic antagonists, vasodilators) to achieve a normalization of blood pressure. The use of additional drugs increases the likelihood of adverse reactions to therapy and complicates the treatment regimen, an effect known to increase non-compliance with hypertension therapy [log, 1091. CLINICAL

IMPLICATIONS

Many of the neural, hormonal. salivary, and structural correlates of pathology can cause changes in gustatory function. Thus, the study of taste may yield insights with respect to the prediction, diagnosis, treatment, and etiologic mechanisms of various health disorders. Findings pertinent to each of these areas are now available in the salt taste/hypertension literature. Before discussing the clinical implications of the available evidence, however, it is important to emphasize the need to exert great caution when relating findings on taste function to clinical practice. The reasons for this are manifold, but include: (1) the lack of standard measures which characterize taste function among individuals with various pathologies. (2) questions concerning the validity of extrapolating findings from data on model tastants to real food systems, or from food models assessed under controlled conditions to free-living situations, and (3) the apparent weak association among measures of taste function and their nebulous relationships to dietary habits. Though answers to many of the questions concerning a relationship between salt taste and hypertension remain elusive, current evidence highlights issues which warrant further investigation, and provides insights of potential clinical value. For example, knowledge of salt preference behavior may aid hypertensives placed on salt restricted diets. While preference for the salty taste, as characterized by current measurement techniques. is not a reliable predictor of salt intake, under choice conditions, the hedonic attributes of different food items do influence selection decisions [45]. Short and long term studies have reported that individuais placed on sodium restricted diets display first a heightened, followed by a diminished preference for the taste. If these findings are substantiated, they may help to explain the widely observed poor compliance with prescribed salt restricted diets [l lo]. Until the hypertensive individual accomodates to a reduced sodium diet, the desire to consume the nutrient may be heightened and serve as one factor undermining the efficacy of this form of therapy. Thus, early rigorous counseling, followed by a less intensive schedule when the patient has adjusted to the new diet, may prove to be the most cost-effective and beneficial counseling approach. The efficacy of non-dietary forms of antihypertensive therapy, such as diuretic treatment, may be improved by considering the literature on salt appetite. Evidence has been presented that diuretics may stimulate or enhance a salt appetite in hypertensives, and thereby result in increased sodium intake. This might compromise the effectiveness of antihypertensive therapy. It would therefore be advisable to alert individuals receiving diuretic treatment to this possible drug action and to provide the patient with early intensive counseling to minimize this effect. The mechanism(s) underlying the development of hypertension remain largely unknown.

204

RICHARD D. MATTES

To date, speculation that aspects of salt taste play a role in the etiology and manifestations of hypertension [1,2] has not been supported. Studies have failed to demonstrate that hypertensives actually consume more salt than normotensives living under similar conditions [89-941 or that salt taste sensitivity, responsiveness, or preference are significantly associated with actual salt intake [37,41,52]. These generally negative findings may reflect the insensitivity of current methodologies for assessing salt intake and taste function in clinical settings. Definitive resolution of this issue awaits the development of improved assessment tools. Future efforts to elucidate a role for taste function and salt intake in the onset and course of hypertension may also benefit by focusing attention on sub-groups of hypertensives who appear to be salt sensitive (i.e. those whose blood pressure is responsive to alterations in salt intake). If measures of salt taste function in some way reflect the metabolism of this nutrient, then the metabolic aberration present in salt sensitive hypertensives could be expected to produce characteristic and distinguishable taste responses. Before such work can be undertaken, however, it will be necessary to develop a reliable method to identify salt sensitive hypertensives. The ability to identify who will develop hypertension before symptoms become manifest remains elusive. Because of the high cost (both economic [ 131and emotional/physical) and prevalence [12] of this disorder, efforts aimed at developing a predictive marker for hypertension must be assigned a high priority by the health care community. Development of such a marker would allow clinicians to intervene via dietary and lifestyle counseling to delay or prevent the onset of chronic high blood pressure levels. Neither salt taste responsiveness nor preference behavior have been found to differ between normotensives and hypertensives in a reliable manner. As a result, measures of these taste parameters offer little promise as predictive markers. There is stronger evidence that hypertensives display altered salt taste sensitivity, as measured by recognition thresholds. The temporal relationship between this apparent shift in sensitivity and the onset of hypertension, however, remains unclear. If the shift in taste function precedes sustained elevations in blood pressure, further study may expedite the development of a much needed predictive marker for this disorder.

CONCLUSION

Physiological and psychological correlates of pathology may be reflected by modifications in the gustatory sense. As a result, assessment of this sensory system, which is often amenable to clinical settings, may provide useful predictive, diagnostic, therapeutic, and mechanistic information about an individual’s impending, current, or past health status. This review highlights a number of findings in the salt taste-hypertension literature of potential clinical relevance. First, there may be a need for intensive dietary counseling of hypertensive patients when they are first placed on either salt restricted diets or diuretics. This point is supported by the evidence indicating that: (1) following a shift to a reduced salt diet there is an apparent transient increase in salt preference and (2) administration of a diuretic may induce a heightened salt appetite in users. Second, a measure of salt taste sensitivity may prove to be of value as a predictive marker for hypertension. Four investigations found hypertensives to present with heightened salt recognition thresholds compared to normotensive controls. The temporal relationship between these shifts in taste function and blood pressure remains unknown. If the taste changes precede those of blood pressure, then the use of a non-invasive, inexpensive, relatively rapid taste measure, amenable to a clinical setting may provide a much needed predictive index for hypertension. Finally, the onset of chronic elevations of blood pressure is not a consequence of alterations of salt taste function and consequent sodium ingestion. No study has demonstrated a significant relationship between a measure of taste function and salt consumption. Furthermore, intra-population studies consistently fail to reveal any significant relationship between salt intake and blood pressure.

Salt Taste and Hypertension

305

The nature of various taste parameters i.e. sensitivity, responsiveness, preference, and appetite was also reviewed along with a consideration of the relationships between these taste attributes and actual dietary habits. It bears reiterating, that while the study of taste may prove valuable to the clinician, great care must be exercised in the interpretation and application of this information. In the past, findings specific to one parameter of the taste sense have been inappropriately generalized to others. The failure to recognize that intake is not based solely, or even primarily, on sensitivity, responsiveness, or preference for a taste quality or food item has resulted in the proposal of dietary prescriptions with uncertain value. While such prescriptions may indeed prove to be of therapeutic value. until tested, it must be assumed that there is a very real possibility that the physical and emotional well-being of individuals prescribed such dietary modifications can be compromised. For example, the inappropriate use of new seasonings or the substitution of different foods in the normal diet of an individual who is ill and anorectic may result in an exacerbation of their dietary problems by further reducing their desire to eat. In addition, it may place added stress on the individual whose previous food habits represent one important emotional tie with normalcy. Acknowledgemenfs-The author would like to express his appreciation to Drs S. K. Kumanyika and B. P. Halpern for their guidance and support and Drs G. Beauchamp, C. Christensen, A. Gilbert and H. Lawless for their critical reading of the manuscript.

REFERENCES

5. 6. 7. 8.

9. IO. il. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24.

Fallis N, Lasagna L, Tetreault L: Gustatory thresholds in patients with hypertension. Nature 196: 7475. 1962 Bisht DB, Krishamurthy M, Rangaswamy R: Studies on threshold of taste for salt with special reference to hypertension. Indian Heart J 23: 137-140, 1971 Schechter PJ, Horwitz D, Henkin RI: Salt preference in patients with untreated and treated essential hypertension. Am J Med Sci 267: 320-326, 1974 Langford HG: Influence of sodium intake on antihypertensive therapy. Cardiovasc Med 93: 843-847. 1973 Carson JAS, Gormican A: Taste acuity and food attitudes of selected patients with cancer. J Am Diet Asaoc 70: 361-365, 1977 DeWys WD, Walters K: Abnormalities of taste sensation in cancer patients. Cancer 36: 1888-1896, 1975 Donaldson SS: Nutritional problems associated with radiation therapy. In Nutrition and Cancer: Etiology and Treatment. Newell GR, Ellison NM (Eds). New York: Raven Press, 1981. pp. 319-337 Porte D, Robertson RP, Walter JB, Kulkosky PJ, Makous WL, Woods SC: Neuroendocrine recognition of glucose: The glucoreceptor hypothesis and the diabetic syndrome. In Food Intake and Chemical Senses. Katuki Y, Sato M, Yakagi SF, Comura Y (Eds), Baltimore: Univ. Park Press, 1977. pp. 331-343 Dye CJ, Koziatek DA: Age and diabetes effects on threshold and hedonic perception of sucrose solutions. J Gerontol 36:310-315, 1981 Wrobel WL, Catalanotto FA, Walter RG: Taste thresholds in caries-free and caries-active navel recruits. Arch Oral Biol 23: 881-885, 1978 Catalanotto FA, Wrobel WR, Epstein DW: Sucrose taste thresholds and dental caries: Implications for dietary counseling. Clin Prev Dent 1: 14-18, 1979 National Institutes of Health: High Blood Pressure Coordinating Committee. New Hypertension Data and Recommended Public Statements. (NIH Pub. No. 79-16231-31), 1979 United States House of Representatives Select Committee on Aging: Treatment of High Blood Pressure in America. Comm. Pub. No. 9&181. Washington, D.C.: Gov’t. Printing Office, 1979. p, 18 Dahl LK: Salt and hypertension. Am J Clin Nutr 25: 231-244, 1972 Gleiberman L. Blood pressure and dietary salt in human populations. Ecol Food Nutr 2: 143-156, 1973 Fries HA: Salt volume and the prevention of hypertension. Circulation 53: 589-595, 1976 Morgan T, Myers J, Carney S: The evidence that salt is an important aetiological, if not the cause. of hypertension. Clin Sci 57: 459+462s, 1979 Tobian L: The relationship of salt to hypertension. Am J Clin Nutr 32: 2739-2748, 1979 Contreras RI: Salt taste and disease. Am J Clin Nutr 31: 1088-1097, 1978 Simpson FO: Salt and hypertension: A skeptical review of the evidence. Clin Sci 57: 463~480s. 1979 O’Mahony M: Salt taste adaptation: The psychophysical effects of adapting solutions and residual stimuli from prior testings on the taste of sodium chloride. Percept 8: 41 l-476, 1979 McBurney DH: Magnitude estimation of the taste of sodium chloride after adaptation to sodium chloride. J Exp Psycho1 72: 869-873, 1960 Langford HG, Watson RL: A study of the urinary sodium, salt-taste threshold and blood pressure resemblance of siblings. Hopkins Med J 131: 143-146, 1972 Wotman S, Mandel ID, Thompson RH, Laragh JH: Salivary electrolytes and salt taste thresholds in hypertension. J Chron Dis 20: 833-840, 1967

206

RICHARD D. MATTES

25. Viskoper RJ, Lugassy G: Elevated taste threshold for salt in hypertensive subjects. Kidney Int 15: 582, 1979 26. Langford HG, Watson RL, Thomas JG: Salt intake, diuretics and the treatment of hypertension. Tram Am Clin Climatol Assoc 88: 32-37, 1976 27. Neidermeier W, Driezen S, Stone RE, Spies TD: Sodium and potassium concentrations in the saliva of normotensive and hypertensive subjects. Oral Surg 9: 426431, 1956 28. Ben-Aryeh H, Schiller M, Shasha S, Szargel R, Gutman D: Salivary composition in patients with essential hypertension and the effect of Pindolol. J Oral Med 36: 7678, 1981 29. Henkin RI:- Salt taste in patients with essential hypertension and with hypertension due to primary hyperaldosteronism. J Chron Dis 27: 2355244, 1974 HG: Salivary sodium correlates with salt recognition threshold. Physiol Behav 30. Mbrino T, Langford 21: 45-48, 1978 31. Lauer RM, Filer LJ, Reiter MA, Clark WR: Blood pressure, salt preference, salt threshold and relative weight. Am J Dis Child 130: 493497, 1976 32. Stevens SS: Sensory scales of taste intensity. Percept Psychophys 6: 302-308, 1969 and psychometric approaches to sensory evaluation. CRC Crit Rev Food 33. Moskowitz HR: Psychophysical Sci Nutr 9:41-79, 1977 LM: The psychophysics of taste. Am J Clin Nutr 31: 106881077, 1978 34. Bartoshuk M, Wingate P: Our industry today: Psychophysical aspects of sensory analysis of dairy 35. O’Mahony products: A critique. J Dairy Sci 62: 1954-1962, 1979 L: Influence of chemoreception and psychologic state on food selection. Int J Obesity 36. Bartoshuk 4: 351-355. 1980 K, Weiss RA: Taste and salt intake in human hypertension. In 37. Bernard RA, Doty RL, Engelman Biological and Behavioral Aspects of Salt Intake. Kare MR, Fregly MJ, Bernard RA (Eds). New York: Academic Press, 1980. pp. 397409 of plasma renin in essential hypertension. JAMA 23 1: 165- 170, 38. Kaplan NM: The prognostic implications 1975 39. Kaplan NM: Renin profiles: The unfulfilled promises. JAMA 238: 61 l-613, 1977 mechanisms of renovascular and essential arterial hypertension. In 40. Page IH: Some regulatory Hypertension. Genest J, Koiw E. Kuchel 0 (Eds). New York: McGraw-Hill, 1977. p. 576 SK, Halpern BP: Salt taste responsiveness and preference among normotensive, 41. Mattes RM, Kumanyika prehypertensive and hypertensive adults. Chemical Senses 8: 2740, 1983 MA, Weinberger MH: Effects of sodium loading 42. Grim CE, Luft FC, Miller JZ, Brown PL, Gannon and depletion in normotensive first-degree relatives of essential hypertensives. J Lab Clin Invest 94: 764771, 1979 PI, Wong 0, Altschul AM: Electrolyte output, blood pressure and family history of 43. Pietinen hypertension. Am J Clin Nutr 32: 997-1005, 1979 HR: Taste and food technology: Acceptability, aethetics and preference. In Handbook of 44. Moskowitz Perception. Carterette EC, Friedman MP (Eds). Vol. VIA, Testing and smelling. New York: Academic Press, 1978. pp. 154194 consumer preference in institutional food service. Food Service Systems. 45. Meiselman HL: Determining New York: Academic Press, 1979. pp. 127-153 L: High salt content of western infant’s diet: Possible relationship to 46. Dahl LK, Heine M, Tassinari hypertension in the adult. Nature 198: 1204-1205, 1963 predisposing factor in hypertension? Am J Clin Nutr 21: 863-867, 1968 47. Guthrie HA: Infant feeding-A on Nutrition, American Academy of Pediatrics: Salt intake and eating patterns of infants 48. Committee and children in relation to blood pressure. Pediatrics 53: 115-121, 1974 49. Filer LJ: Salt in infant foods. Nutr Rev 29: 27-30, 1971 50. Whitten CF, Stewart RA: The effect of dietary sodium in infancy on blood pressure and related factors: Studies of infants fed salted and unsalted diets for five months at eight months and eight years of age. Acta Paediatr Stand 279 (Suppl): 2-17, 1980 In Epidemiology of Hypertension. Stamler J, Stamler R, Pullman TN (Eds). New 51. Paul 0: Discussion. York: Grune and Stratton, 1967. pp. 248-249 RM, Pecore SD: Taste perception of sodium chloride in relation to dietary intake of salt. 52. Pangborn Am J Clin Nutr 35: 510-520, 1982 food acceptance. J Food Sei 30: 365-374, 1965 53. Schutz HG: Food action rating scale for measuring 1958 54. Dahl LK: Salt intake and salt need. N Engl J Med 258: 1152-1157, P, Kebede J: Lack of response of salt taste threshold and preference 55. Gillum RF, Prineas RJ, Anderson to dietary sodium restriction in mild hypertension. Am Heart J 102: 138, 1981 GK, Engelman K: Long-term reduction in dietary sodium alters the taste of 56. Bertino M, Beauchamp salt. Am J Clin Nutr 36: 1134-l 144, 1982 GK, Riskey DR, Engelman K: Taste perception in three individuals on a low 57. Bertino M, Beauchamp sodium diet. Appetite 2: 67-73, 1981 basis of sodium appetite: A new look at the “depletion-repletion” model. 58. Stricker EM: The physiological In Biological and Behavioral Aspects of Salt Intake. Kare MR, Fregly MJ, Bernard RA (Eds). New York: Academic Press, 1980. pp. 1855202 59. Denton D: Instinct, appetites and medicine. Aust NZ J Med 2: 203-212, 1972 60. Green HH: Perverted appetites. Physiol Rev 5: 336348, 1925 FJ. Ward A: Appetite and choice of diet: The ability of the vitamin 61. Harris LJ, Clay J, Hargreaves deficient rat to discriminate between diets containing and lacking the vitamin. Proc R Sot London Ser B 113: 161-190, 1933 1943 62. Hull CL: Principles of Behavior. New York: Appleton-Century, 63. Kaunitz H: Causes and consequences of salt composition. Nature 178: 1141-I 144, 1956

Salt Taste 64. 65. 66. 67. 68. 69. 70. 71. 72. 73. 74. 75. 76. 77. 78. 79. 80. 81. 82. 83. 84. 85.

86. 87. 88. 89.

90. 91. 92.

93. 94.

95. 96. 97 98 99. too

and Hypertension

207

Young PT: The role of affective processes in learning and motivation. Psycho1 Rev 66: 104-125, 1959 Nachman M: Taste preference for sodium salts by adrenalectomized rats. J Comp Physiol Psycho1 55: 1124-l 129, 1962 Wolf G: Innate mechanisms for regulation of sodium intake. In Olfaction and Taste. Pfaffman C (Ed.). New York: Rockefeller Univ. Press, 1969, pp. 548-553 Schulkin J: Mineralocorticoids, dietary conditions and sodium appetite. Behav Biol 23: 197-205, 1978 Wolf G, McGovern JF, DiCara LV: Sodium appetite: Some conceptual and methodologic aspects of a model drive system. Behav Biol IO: 27-42, 1974 Jalowiec JE: Sodium appetite elicited by Furosemide: Effects of differential dietary maintenance. Jkhav Biol 10: 313-327, 1974 Buggy J, Fisher AE: Evidence for a dual central role for angiotensin in water and sodium intake. Nature 250: 733-735, 1974 Fitzsimons JT: Thirst and sodium appetite. Endeavour 4: 97-101, 1980 Fregly MJ, Harper JM Jr, Radford EP Jr: Regulation of sodium chloride intake by rats. Am J Physiol 209: 287-292, 1965 Richter CP. Salt appetite of mammals: Its dependence on instinct and metabolism. In L’lnstinct dans le Comportement des Animaux et de I’Homme. Paris: Masson, 1956. pp. 577-632 Morrison GR, Young JC: Taste control over sodium intake in sodium deficient rats. Psycho1 Behav 8: 29-32, 1972 DiCara LV, Wilson LM: Role of gustation in sodium appetite. Physiol Psycho1 2: 43-44, 1974 Denton DA: Sodium and hypertension. In Mechanisms of Hypertension. Sambhi M (Ed.). New York: Elsevier, 1973. pp. 4654 Wilkins L, Richter CP: A great craving for salt by a child with corticoadrenal insufficiency. JAMA 114: 866888, 1940 Thorn GW. Dorrance SS, Day E: Addison’s disease: Evaluation of synthetic desoxycorticosterone acetate therapy in 158 patients. Ann Int Med 16: 1053-1096, 1942 Liddle GW: The adrenals, Part I-The adrenal cortex. In Textbook of Endocrinology. Williams RH (Ed.). Philadelphia: W. B. Saunders, 1974. pp. 233-282 Beauchamp GK, Maller 0: The development of flavor preferences in humans: A review. In The Chemical Senses and Nutrition. Kare MR, Mailer 0 (Eds.). New York: Academic Press, 1977. pp. 291-310 Holmberg AR: Nomads of the longbow. Smithson Inst Sot Anthropol Wash., DC. No. IO, p. 35 Kroeber AL: Cultural element distribution XV. Salt. dogs, tobacco. Berkeley Anthropol Ret 6: l-20. 1942 Lowenstein FW: Blood pressure in relation to age and sex in the tropics and subtropics. A review of the literature and an investigation in two tribes of Brazil Indians. Lancet I: 389-392. 1961 Maddocks I: Blood pressures in Melanesians. Med J Aust I: 1123-l 126, 1967 Sinnet PF, Whyte HM: Epidemiological studies in a total highland population. Tukisenta, New Guinea: cardiovascular disease and relevant clinical electrocardiographic, radiological and biochemical tindings. J Chron Dis 26: 265-290, 1973 Oliver WJ, Cohen EL, Neel JV: Blood pressure, sodium intake, and sodium related hormones in the Yanomamo Indians, A “no-salt” culture. Circulation 52: 14&151, 1975 Senate Select Committee on Nutrition and Human Needs: Dietary Goals for the United States, revised edn. Wash., D.C.: U.S. Gov’t Printing Office, 1977 U.S. Dept. of Agriculture: Nutrition and your Health: Dietary Guidelines for Americans. Wash.. D.C.: U.S. Dept. of Agri. and U.S. DHEW, 1980 Dawber TR, Kannel WB, Kagan A, Donabidian RK, McNamara PM, Person G: EnvIronmental factors in hypertension. In Epidemiology of Hypertension. Stamler J, Stamler R, Pullman TN (Eds). New York: Grune and Stratton, 1967. pp. 255-282 Swaye PS. Gifford RW, Berrettoni JN: Dietary salt and essential hypertension. Am J Cardiol 29: 33-38. 1972 Morgan T, Adam W. Gillies A, Wilson M, Morgan G, Carney S: Hypertension treated by salt restriction. Lancet I: 227-230, 1978 Liu K. Cooper R. McKeever J, McKeever P, Byington R, Soltero I, Stamler R, Gosch F. Stevens E. Stamler J: Assessment of the association between habitual salt intake and high blood pressure: methodological problems. Am J Epid 110: 219-226, 1979 Schlierf G: Arab L, Schellenberg -B, Oster P, Mordasini R, Schmidt-Gayk H, Vogel G: Salt and hvoertension. Data from the Heidelberg studv. Am J Clin Nutr 33: 872-875, 1980 Tiomilehto J, Karppanen H, Tanskane; A, Tikkanen J, Vuori J: Sodium and potassium excretion m a sample of normotensive and hypertensive persons in Eastern Finland. J Epid Commun Hlth 34: 174-178, 1980 Fregly MJ, Kim KJ: Specificity of the sodium chloride appetite of hydrochlorthiazide treated rats. Physiol Behav 5: 595-599, 1970 Parijs J, Joosens JV, Linden LV, Verstreken G, Amery AKP: Moderate sodium restriction and diuretics m the treatment of hypertension. Am Heart J 85: 22-34, 1973 Langford HG, Watson RL, Thomas JG: Salt intake and the treatment of hypertension. Am Heart J 93: 531-532, 1977 Rock CL. Hall WD: Dietary salt intake increases with thiazide therapy. Am Fam Physician 17: 207. 1978 Liu K, Dyer AR, Cooper RS, Stamler J: Can overnight urine replace 24-hour urine collection to assess salt intake? Hypertension I: 529-536, 1979 Yamori Y, Masahiro K, Fujikawa J, Soh Y, Nara Y, Ohtaka M, Horie R, Tsunematsu T. Note S. Fukase M: Dietary risk factors of stroke and hypertension in Japan Part I: Methodological assessment of urialysis for dietary salt and protein intakes. Jap Circ J 46: 933-938, 1982

RICHARD

208 101.

D.

MATTFS

Luft FC, Fineberg NS, Sloan RS: Overnight urine collections to estimate sodium intake. Hypertension 4: 494-498,

1982

102. Luft FC, Fineberg NS, Sloan RS: Estimating dietary sodium intake in individuals receiving a randomly fluctuating intake. Hypertension 4: 805-808, 1982 103. Bing RF, Thurston H, Swales JD: Salt intake and diuretic treatment of hypertension. Lancet 2: 121-123, 1979 104. Levine B, Chan MM: The effect of the withdrawal of diuretics on the preference for salt, the perception of salt intensity and the sodium intake of well-controlled, free-living hypertensive individuals. 5th Ann Meet Assoc for Chemoreception Sciences. Sarasota, Fla. April 27-May I, 1983 Fallis N, Ford RV: Electrolyte excretion and hypotensive response. JAMA 176: 581-584, 1961 105. 106. Finnerty FA, Davidon d, Kakaviatos N: Relation of sodium balance to arterial pressure during drug-induced saluresis. Circulation 37: 175-183, 1968 107. Winer BM: The antihypertensive actions of benzothiazides. Circulation 23: 21 I-218, 1961 108. Podel RN: Physicians Guide to Compliance in Hypertension. New York: Merck and Company, 1975 109. Finnerty FA: The problem of non-compliance. Med Times 106: 71-75, 1978 110. Kris-Etherton PM, Kisloff L, Kassouf RA, Rogers C: Teaching principles and cost of sodium restricted diets. J Am Diet Assoc 80: 55-58, 1982