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TABLE 1 Dietary Reference Intakes for Sodium and Chloride by Life Stage Group DRI values (g/day) Sodium Chloride AIa ULb AI UL Life stage groupc NDd 0 through 6 mo 0.12 0.18 ND 7 through 12 mo 0.37 ND 0.57 ND 1 through 3 y 1.0 1.5 1.5 2.3 4 through 8 y 1.2 1.9 1.9 2.9 9 through 13 y 1.5 2.2 2.3 3.4 14 through 18 y 1.5 2.3 2.3 3.6 19 through 30 y 1.5 2.3 2.3 3.6 31 through 50 y 1.5 2.3 2.3 3.6 51 through 70 y 1.3 2.3 2.0 3.6 > 70 y 1.2 2.3 1.8 3.6 Pregnancy £18 y 1.5 2.3 2.3 3.6 19 through 50 y 1.5 2.3 2.3 3.6 Lactation £18 y 1.5 2.3 2.3 3.6 19 through 50 y 1.5 2.3 2.3 3.6 a AI = Adequate Intake. b UL = Tolerable Upper Intake Level. Unless otherwise specified, the UL represents total intake from food, water, and supplements. c All groups except Pregnancy and Lactation represent males and females. d ND = Not determinable. This value is not determinable due to the lack of data of adverse effects in this age group and concern regarding the lack of ability to handle excess amounts. Source of intake should only be from food to prevent high levels of intake.

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PART III: SODIUM AND CHLORIDE 387 SODIUM CHLORIDE AND S odium and chloride are necessary to maintain extracellular fluid volume and plasma osmolality. The cation sodium and the anion chloride are normally found in most foods together as sodium chloride (salt). For this reason, this publication presents data on the requirements for and the effects of sodium and chloride together. Since data were inadequate to determine Estimated Average Requirements (EARs) and thus calculate Recommended Dietary Allowances (RDAs) for so- dium and chloride, Adequate Intakes (AIs) were instead developed. The AIs for sodium are set at an intake that ensures that the overall diet provides an ad- equate intake of other important nutrients and covers sodium sweat losses in unacclimated individuals who are exposed to high temperatures or who be- come physically active. The AIs for chloride are set at a level equivalent on a molar basis to that of sodium, since almost all dietary chloride comes with sodium added during the processing or consumption of foods. The AIs for sodium do not apply to individuals who lose large volumes of sodium in sweat, such as competitive athletes and workers exposed to extreme heat stress (e.g., foundry workers and firefighters). The adverse effects of higher levels of sodium intake on blood pressure provide the scientific rationale for setting the Tolerable Upper Intake Level (UL) for sodium and chloride. DRI values are listed by life stage group in Table 1. In the United States, sodium chloride accounts for about 90 percent of total sodium intake in the United States. Most of the sodium chloride found in the typical diet is added to food during processing. Examples of high-sodium processed foods include luncheon meats and hot dogs, canned vegetables, pro- cessed cheese, potato chips, Worcestershire sauce, and soy sauce. Overall, there is little evidence of any adverse effect of low dietary sodium intake on serum or plasma sodium concentrations in healthy people. Likewise, chloride deficiency is rarely seen because most foods that contain sodium also provide chloride. The primary adverse effect related to increased sodium chlo- ride intake is elevated blood pressure, which is directly related to cardiovascu- lar disease and end-stage renal disease. Individuals with hypertension, diabe- tes, and chronic kidney disease, as well as African Americans and older people, tend to be more sensitive than others to the blood pressure–raising effect of sodium chloride intake.

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DRIs: THE ESSENTIAL GUIDE TO NUTRIENT REQUIREMENTS 388 SODIUM AND CHLORIDE AND THE BODY Function About 95 percent of the body’s sodium content is found in the extracellular fluid, where it serves as the primary cation. Sodium regulates extracellular fluid volume and plasma volume and also plays an important role in the membrane potential of cells (the electrical potential difference across a cell’s plasma mem- brane) and the active transport of molecules across cell membranes. Chloride, in association with sodium, is the primary osmotically active anion in the extracellular fluid. It plays a key role in maintaining fluid and electrolyte balance. In addition, chloride, in the form of hydrochloric acid, is an important component of gastric juice. Absorption, Metabolism, Storage, and Excretion Sodium and chloride ions are typically consumed as sodium chloride. About 98 percent of ingested sodium chloride is absorbed, mainly in the small intes- tine. Absorbed sodium and chloride remain in the extracellular compartments, which include the plasma, interstitial fluid, and plasma water. As long as sweat- ing is not excessive, most of this sodium chloride is excreted in the urine. In people with “steady-state” sodium and fluid balance, and minimal sweat loss, the amount of sodium excreted in urine is roughly equal to the amount con- sumed, when other obligatory sodium losses are small. A number of systems and hormones influence sodium and chloride bal- ance, some of which are shown in Table 2. DETERMINING DRIS Determining Requirements Since data were inadequate to determine EARs and thus calculate RDAs for sodium and chloride, AIs were instead developed. The AIs for sodium are set at an intake that ensures that the overall diet provides an adequate intake of other important nutrients and also covers sodium sweat losses in unacclimated indi- viduals who are exposed to high temperatures or who become physically active (as recommended in Part II, “Physical Activity”). The AIs for chloride are set at a level equivalent on a molar basis to that of sodium, since almost all dietary chloride comes with the sodium added during processing or consumption of foods. Concerns have been raised that a low level of sodium intake adversely affects blood lipids, insulin resistance, and cardiovascular disease risk. How- ever, at the level of the AI, the preponderance of evidence does not support this

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PART III: SODIUM AND CHLORIDE 389 TABLE 2 Major Systems and Hormones That Influence Sodium Chloride Balance System or Hormones Activators Effect Renin-angiotensin- • Reduced salt intake • Promotes retention of sodium aldosterone axis • Reduced blood volume and chloride by the kidneys • Reduced blood pressurea • Promotes renal reabsorption of sodium Atrial natriuretic peptide • Elevated blood volume • Increases glomerular filtration (counter-regulatory system • Increased salt intake rate to renin-angiotensin- • Increased blood pressure • Reduces blood volume aldosterone axis) • Reduces blood pressure • Increases sodium excretion Sympathetic nervous • Reduced salt intake • Reduces sodium reabsorption system • Reduced blood volume • Reduces water reabsorption in • Reduced blood pressure the kidneys a When the renin-angiotensin-aldosterone system is less responsive, as with advanced age, a greater decrease in blood pressure results from reduced sodium chloride intake. contention. A potential indicator of an adverse effect of inadequate sodium is an increase in plasma renin activity. However, in contrast to the well-accepted benefits of blood pressure reduction, the clinical relevance of modest rises in plasma renin activity as a result of sodium reduction is uncertain. It is well recognized that the current intake of sodium for most individuals in the United States and Canada greatly exceeds both the AI and the UL. Progress in achieving a reduced sodium intake will likely be gradual, requiring changes in personal behavior toward salt consumption, which includes the replacement of high sodium foods with lower sodium alternatives, as well as increased col- laboration between the food industry and public health officials. Also required will be a broad spectrum of additional research that includes the development of reduced sodium foods that maintain flavor, texture, consumer acceptability, and low cost. Special Considerations Excessive sweat loss: The AI for sodium does not apply to individuals who lose large volumes of sodium in sweat, such as competitive athletes and workers exposed to extreme heat stress (e.g., foundry workers and firefighters).

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DRIs: THE ESSENTIAL GUIDE TO NUTRIENT REQUIREMENTS 390 Criteria for Determining Sodium and Chloride Requirements, by Life Stage Group Life stage group Criterion 0 through 6 months Average consumption of sodium from human milk 7 through 12 months Average consumption of sodium from human milk + complementary foods 1 through 18 y Extrapolation of adult AI based on median energy intake level from CSFII 19 though 50 y Intake level to cover possible daily losses, provide adequate intakes of other nutrients, and maintain normal function > 50 y Extrapolation from younger adults based on median energy intake level from CSFII Pregnancy < 18 through 50 y Age-specific AI Lactation < 18 through 50 y Age-specific AI The UL The Tolerable Upper Intake Level (UL) is the highest level of daily nutrient intake that is likely to pose no risk of adverse effects for almost all people. Members of the general population should not routinely exceed the UL. The major adverse effect of increased sodium chloride intake is elevated blood pres- sure. High blood pressure has been shown to be a risk factor for heart disease, stroke, and kidney disease. The scientific rationale for setting the UL is based on the impact of sodium on blood pressure and represents total intake from food, water, and supple- ments. However, because the relationship between sodium intake and blood pressure is progressive and continuous without an apparent threshold, it is difficult to precisely set a UL, especially since other environmental factors (weight, exercise, potassium intake, dietary pattern, and alcohol intake) and genetic factors also affect blood pressure. There was inadequate evidence to support a different upper level of sodium intake in pregnant women from that of nonpregnant women as a means to prevent hypertensive disorders of preg- nancy. Data from the Third National Health and Nutrition Examination Survey (NHANES III, 1988–1994) indicated that more than 95 percent of men and 75 percent of women in the United States consumed sodium chloride in excess of the UL. According to NHANES III, 24.7 percent of men and 24.3 percent of

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PART III: SODIUM AND CHLORIDE 391 women aged 18 years and older had hypertension, indicating that a substantial number of individuals appear to experience this adverse effect. Data on Canadian consumption indicated that 90–95 percent of younger men (aged 19 to 50 years) and between 50 and 75 percent of younger women in the same age range had usual intakes above the UL. Neither of these surveys included discretionary salt usage (e.g., from the salt shaker). Special Considerations: Sensitive individuals: The UL may be even lower for people whose blood pres- sure is most sensitive to increased sodium intake (e.g., older people; African Americans; and individuals with hypertension, diabetes, or chronic kidney dis- ease) and who also have an especially high incidence of heart disease related to high blood pressure. Physical activity and temperature: In contrast, people unaccustomed to pro- longed strenuous physical activity in a hot environment may have sodium needs that exceed the UL because of sodium loss through sweat. DIETARY SOURCES OF SODIUM AND CHLORIDE Foods Sodium chloride (salt) accounts for about 90 percent of total sodium intake in the United States. As Table 3 shows, most of the sodium chloride found in the typical diet is added to food during processing. Because salt is naturally present in only a few foods, such as celery and milk, the reduction of dietary salt does not cause diets to be inadequate in other nutrients. Although sodium chloride is the primary source of dietary sodium, other forms often found in foods as food additives include monosodium TABLE 3 Sources of Dietary Sodium Chloride Percent of Total Source of Salt Sodium Chloride Intake Added to food during processing 77 Naturally occurring in foods 12 Added while eating 6 Added during cooking 5 Tap water <1

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DRIs: THE ESSENTIAL GUIDE TO NUTRIENT REQUIREMENTS 392 glutamate, sodium benzoate, sodium nitrite, and sodium acid pyrophosphate. Sodium bicarbonate and sodium citrate are found in many antacids, which are sometimes consumed in large amounts. Foods that are processed or canned tend to have high levels of additives that contain sodium. Examples include luncheon meats and hot dogs, canned vegetables, processed cheese, and potato chips. Condiments such as Worcestershire sauce, soy sauce, and ketchup also contain substantial amounts of sodium. Dietary Supplements This information was not provided at the time the DRI values for this nutrient were set. Bioavailability This information was not provided at the time the DRI values for this nutrient were set. Dietary Interactions There is evidence that sodium and chloride may interact with certain other nutrients and dietary substances (see Table 4). INADEQUATE INTAKE AND DEFICIENCY Overall, there is little evidence of any adverse effect of low dietary sodium in- take on serum or plasma sodium concentrations in healthy people. Chloride loss usually accompanies sodium loss. Excess chloride depletion causes hy- pochloremic metabolic alkalosis, a syndrome seen in individuals with signifi- cant vomiting. In such cases, the chloride depletion is mainly due to the loss of hydrochloric acid. However, chloride deficiency is rarely seen in healthy people because most foods that contain sodium also provide chloride. Special Considerations Physical activity and temperature: Extremely vigorous physical activity per- formed in high temperatures can potentially affect sodium chloride balance due to the loss of sodium through sweat. The loss depends on a number of factors, including overall diet, sodium intake, sweating rate, hydration status, and one’s degree of acclimation to the heat. People who are accustomed to heat exposure lose less sodium through their sweat than those unaccustomed to high temperatures.

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PART III: SODIUM AND CHLORIDE 393 TABLE 4 Potential Interactions with Other Dietary Substances Substance Potential Interaction Notes SUBSTANCES THAT AFFECT SODIUM AND CHLORIDE Potassium Increased potassium intake Potassium may inhibit sodium reabsorption in the increases urinary excretion kidneys, thereby reducing extracellular fluid and of sodium chloride and blunts plasma volumes. This is considered to be an the rise in blood pressure important aspect of the antihypertensive effect of resulting from excess sodium potassium. intake. SODIUM AND CHLORIDE AFFECTING OTHER SUBSTANCES Sodium: Sodium:potassium ratio is Clinical trials have shown that increased potassium potassium typically more closely intake lowers blood pressure, and the effects of ratio associated with blood potassium in reducing blood pressure appear to be pressure than the intake greatest when sodium is concurrently high. Increased of either substance alone, potassium intake also reduces the sensitivity of blood especially in older adults. pressure changes to sodium intake. The incidence of kidney Currently, there are not enough data to set different stones has been shown to intake recommendations based on the increase with an increased sodium:potassium ratio. sodium:potassium ratio. Diuretics: Diuretics increase urinary excretion of water, sodium, and chloride, some- times causing low blood levels of sodium (hyponatremia) and chloride (hypo- chloremia). Some people have experienced severe hyponatremia as a result of taking thiazide-type diuretics. However, this appears to be due to impaired water excretion rather than excessive sodium loss since it can be corrected by water restriction. Cystic fibrosis: This genetic disorder is characterized by the body’s production of abnormally thick, viscous mucus due to the faulty membrane transport of sodium chloride. As a result, the sodium and chloride content of sweat is very high. Although the increased amount of sodium and chloride required by people with cystic fibrosis is unknown, the needs are particularly high for those who exercise and therefore lose additional sodium and chloride through sweat. Diabetes: High blood glucose levels increase renal excretion of sodium and water. In instances of acute hyperglycemia (e.g., diabetic ketoacidosis), low blood

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DRIs: THE ESSENTIAL GUIDE TO NUTRIENT REQUIREMENTS 394 levels of sodium may occur and can generally be treated with intravenous so- dium chloride and water along with insulin. Some hypoglycemic medications, such as chlorpropramide, have been associated with low blood sodium levels. In some elderly people with diabetes, hyporeninemic hypoaldosteronism may increase renal sodium loss. EXCESS INTAKE The major adverse effect of increased sodium chloride intake is elevated blood pressure, which has been shown to be an etiologically related risk factor for cardiovascular and renal diseases. On average, blood pressure rises progres- sively with increased sodium chloride intake. The dose-dependent rise in blood pressure appears to occur throughout the spectrum of sodium intake. How- ever, the relationship is nonlinear in that the blood pressure response to changes in sodium intake is greater at sodium intakes below 2.3 g/day than above this level. The strongest dose–response evidence comes from clinical trials that specifically examined the effects of at least three levels of sodium intake on blood pressure. The range of sodium intake in these studies varied from 0.23 to 34.5 g/day. Several trials included sodium intake levels close to 1.5 g/day and 2.3 g/day. Special Considerations Special populations: Although blood pressure, on average, rises with increased sodium intake, there is well-recognized heterogeneity in the blood pressure response to changes in sodium chloride intake. Individuals with hypertension, diabetes, and chronic kidney disease, as well as older people and African Ameri- cans, tend to be more sensitive to the blood-pressure-raising effects of sodium chloride intake (defined as salt sensitivity) than others. Genetic factors also influence the blood pressure response to sodium chloride. There is considerable evidence that salt sensitivity is modifiable. In research studies, different techniques and quantitative criteria have been used to define salt sensitivity. In general terms, salt sensitivity is expressed as either the reduc- tion in blood pressure in response to a lower salt intake or the rise in blood pressure in response to sodium loading. Salt sensitivity differs among popula- tion subgroups and among individuals within a subgroup. The rise in blood pressure from increased sodium chloride intake is blunted in the setting of a diet that is high in potassium or low in fat, and rich in miner- als. Nonetheless, a dose–response relationship between sodium intake and blood pressure still persists. In nonhypertensive individuals, a reduced salt intake can decrease the risk of developing hypertension (typically defined as systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥ 90 mm Hg).

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PART III: SODIUM AND CHLORIDE 395 KEY POINTS FOR SODIUM AND CHLORIDE Sodium and chloride are necessary to maintain extracellular 3 fluid volume and plasma osmolality. The cation sodium and the anion chloride are normally found in most foods together as sodium chloride (salt). About 98 percent of the sodium chloride consumed is absorbed. Since data were inadequate to determine EARs and thus 3 calculate RDAs for sodium and chloride, AIs were instead developed. The AIs for sodium are set at an intake that ensures that the 3 overall diet provides an adequate intake of other important nutrients and also covers sodium sweat losses in unacclimated individuals who are exposed to high temperatures or who become physically active. The AIs for chloride are set at a level equivalent on a molar basis to that of sodium. The UL is set based on the impact of sodium on blood pressure. It is well recognized that the current intake of sodium for most 3 individuals in the United States and Canada greatly exceeds both the AI and the UL. There is inadequate evidence to support a different upper 3 intake level of sodium intake in pregnant women from that of nonpregnant women as a means to prevent hypertensive disorders of pregnancy. The UL may be even lower among people whose blood 3 pressure is most sensitive to increased sodium intake (e.g., older persons; African Americans; and individuals with hypertension, diabetes, or chronic kidney disease) and who also have an especially high incidence of heart disease related to high blood pressure. In contrast, people who are not accustomed to prolonged 3 strenuous physical activity in a hot environment may have sodium needs that exceed the UL because of sodium losses through sweat. Sodium chloride (salt) accounts for about 90 percent of total 3 sodium intake in the United States. Most of the sodium chloride found in the typical diet is added to food during processing. Examples include luncheon meats and hot dogs, canned vegetables, processed cheese, and potato chips. Condiments such as Worcestershire sauce, soy sauce, and ketchup also contain substantial amounts of sodium.

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DRIs: THE ESSENTIAL GUIDE TO NUTRIENT REQUIREMENTS 396 There is little evidence of any adverse effect of low dietary 3 sodium intake. Chloride deficiency is rarely seen because most foods that contain sodium also provide chloride. Diuretics increase urinary excretion of water, sodium, and 3 chloride, sometimes causing low blood levels of sodium (hyponatremia) and chloride (hypochloremia). The primary adverse effect related to excessive sodium 3 chloride intake is high blood pressure, which is a risk factor for heart disease, stroke, and kidney disease. On average, blood pressure rises progressively with increased 3 sodium chloride intake. However, this relationship is nonlinear.