Salt intake and hypertension

INTRODUCTION — Sodium, commonly consumed as sodium chloride (table salt), is a major component of our food supply. Although sodium can be consumed in nonchloride forms (sodium bicarbonate [ie, baking soda] and monosodium glutamate [MSG]), salt provides approximately 90 percent of dietary sodium [1]. In the United States, the quantity of sodium is typically reported as milligrams or millimoles of sodium, whereas in other parts of the world, in the scientific literature, and in recommendations, the quantity of sodium is reported as grams of salt (sodium chloride) rather than as sodium alone (to convert between units: grams of salt x 393 = milligrams of sodium; millimoles of sodium x 23 = milligrams of sodium).

The relationship between sodium intake and blood pressure (BP), as well as the effects of sodium reduction in patients with uncomplicated primary hypertension (formerly called "essential" hypertension), are discussed in this topic review.

The importance of a reduced sodium intake, as well as fluid removal with diuretics, for volume management BP control in patients with chronic kidney disease is discussed elsewhere:

●(See "Overview of hypertension in acute and chronic kidney disease", section on 'Benefits of sodium restriction'.)

●(See "Antihypertensive therapy and progression of nondiabetic chronic kidney disease in adults", section on 'Importance of salt intake'.)

The relationship of other factors to the development of hypertension, the evaluation of the hypertensive patient, and the management of hypertension in general and in specific subpopulations are discussed elsewhere:

●(See "Overview of hypertension in adults".)

●(See "Initial evaluation of adults with hypertension".)

●(See "Choice of drug therapy in primary (essential) hypertension".)

●(See "Goal blood pressure in adults with hypertension".)

SODIUM INTAKE IN THE POPULATION — Humans have the capacity to survive at extremes of sodium intake from <200 mg (10 mmol)/day of sodium in the Yanomami Indians of Brazil to >10,300 mg (450 mmol)/day in Northern Japan [2]. The ability of humans to survive at extremely low levels of sodium intake reflects the capacity of the normal human body to conserve sodium by markedly reducing losses of sodium in the urine and sweat. In a steady state, the minimal amount of sodium required to replace losses is estimated to be 180 mg (8 mmol)/day [3].

Sodium consumption in the United States and Europe is high [4,5]. As an example, based upon data from the National Health and Nutrition Examination Survey study, the estimated average sodium intake in the United States is approximately 3600 mg/day [4], which exceeds both the recommended upper limit of 2300 mg/day set by the 2015 United States Dietary Guidelines [6] and the more stringent limit of 1500 mg/day set by the American Heart Association [7]. Average intake is approximately 4200 mg/day in men and approximately 3000 mg/day in women. The greater consumption of sodium in men compared with women results largely from the fact that sodium intake is highly correlated with total food intake, and men consume substantially more than women, especially in young and middle-age years (figure 1).

While many people enjoy the taste of salt, the taste for salt is malleable and decreases as people are gradually exposed to a lower-sodium diet [8]. Because of its ubiquity in the food supply, even motivated consumers find it difficult to reduce their salt intake. Approximately 80 percent of sodium intake in the United States comes from restaurant and packaged food, while a substantially smaller amount comes from discretionary sources (ie, added by individuals during meals and food preparation) (figure 2) [1].

SCIENTIFIC RATIONALE FOR DIETARY SODIUM REDUCTION — Blood pressure (BP)-related diseases (eg, coronary heart disease, stroke, heart failure, and end-stage kidney disease [ESKD]) are leading causes of morbidity and mortality throughout the world [9]. The risk of BP-related diseases increases progressively throughout the range of BP, including both the nonhypertensive and hypertensive ranges [10]. An estimated 47 percent of coronary heart disease events and 54 percent of strokes can be attributed to elevated BP [9]. A fundamental aspect of the elevated BP epidemic is the age-related rise in BP in both children and adults.

The level of BP in an individual and, more broadly, in a population reflects a combination of multiple influences: genetic factors that raise BP and others that lower BP, environmental factors (eg, diet, weight), physiologic characteristics (eg, age), and clinical factors (eg, kidney function). Of these, diet, including sodium intake, is one of the few determinants of BP that individuals can modify.

Effect of sodium on blood pressure — Excess sodium intake has an important, if not predominant, role in the pathogenesis of elevated BP [11]. Supportive evidence comes from animal studies, migration studies, ecologic studies, longitudinal observational studies, clinical trials, meta-analyses of trials, and genetic studies. (See "Genetic factors in the pathogenesis of hypertension", section on 'Monogenic (secondary) hypertension'.)

Dietary sodium reduction lowers BP in nonhypertensive and hypertensive individuals, across the lifespan from children [12] to older-aged persons [13]. Over 100 trials have examined the relationship between sodium intake and BP. The best available evidence strongly indicates a direct relationship between sodium intake and elevated BP; on average, as sodium intake is reduced, BP is also reduced [14-16]. In general, the magnitude of the BP reduction as a result of reduced sodium intake is greater in Black patients [17-19], middle- and older-aged persons, individuals with hypertension (with larger effects in patients who have more severe hypertension) [16,17,20], and, likely, also in patients with diabetes or kidney disease. Although BP reductions observed in children and nonhypertensive adults in response to sodium reduction are small, the best available evidence suggests that a reduced sodium intake can delay and potentially prevent the onset of hypertension [21] and, thereby, potentially reduce the risk of cardiovascular disease [22]. (See 'Effects of sodium on cardiovascular disease' below.)

Dietary sodium reduction also blunts the age-related rise in BP. Because BP rises with age, approximately 90 percent of adults eventually become hypertensive [23]. Numerous studies, including the Dietary Approaches to Stop Hypertension (DASH)-Sodium trial have demonstrated that sodium reduction lowers BP more in older adults than in younger adults [17]. As an example, in persons without hypertension, BP decreased by 7 mmHg in those >45 years of age compared with 3.7 mmHg in those ≤45 years of age. These results indicate that dietary sodium reduction has the potential to lessen the rise in BP with age and also confirm the well-documented observation that members of isolated populations (eg, Yanomami Indians) who consume a low-sodium diet have a smaller age-related rise in BP than those in populations with higher sodium intake [24,25].

In addition to trials that focused on lowering sodium intake, a number of trials have documented that replacing conventional table salt with potassium-enriched salt substitutes also lowers BP [26,27]. In a meta-analysis of randomized trials, salt substitutes lowered systolic/diastolic BP by a mean of 4.6/1.6 mmHg [28]. However, efforts to increase awareness and availability of potassium-enriched salt substitutes are warranted, given that salt substitutes are not commonly used in most countries [29].

Variability in the blood pressure response to sodium — The BP response to a change in salt (sodium chloride) intake is heterogeneous. "Salt sensitivity" is the term that has been applied to this quantitative (ie, continuous) trait. Those persons who exhibit the largest rise in BP in response to increased sodium intake (and the largest fall in BP in response to decreased sodium intake) have been termed "salt sensitive" (SS), while those who exhibit little or no BP change have been termed "salt resistant" (SR). Defining an individual as SS or SR depends upon the use of arbitrarily chosen cutoffs for the magnitude of the BP change as well as the magnitude of the change in sodium, and there is no widely accepted threshold that denotes salt sensitivity. Using a large cutoff for the BP change (eg, a systolic BP increase of >10 mmHg) will lead to few persons being classified as SS; by contrast, using a small threshold (eg, a systolic BP increase of >0 mmHg) will lead to a substantial fraction of persons being classified as SS.

The heterogeneous BP response to an increased sodium intake may reflect true biologic differences among individuals, random variability and imprecision of BP measurements, or both. BP measurements in an individual in a steady state are highly variable, and, therefore, many of the observed differences in BP response to sodium likely represent random variation (ie, measurement error). However, many studies, mostly performed in rodents, suggest that true underlying biologic differences are also likely to contribute [30]. Most genetic abnormalities detected to date in SS hypertensive rodents relate to the regulation of natriuresis. Indeed, most mechanistic studies have implicated subclinical kidney dysfunction, particularly renal handing of sodium excretion, as one cause of salt sensitivity [31]. However, other pathways, including regulation of regional blood flows [32], cutaneous sodium storage, and innate immunity, are emerging, in large part from research using modern techniques of genetic investigation [33-35].

Human studies suggest that age, race-ethnicity, sex, adiposity, and certain clinical conditions (hypertension, diabetes, and chronic kidney disease) might influence the BP response to salt. For several of these factors, evidence is insufficient to draw strong conclusions because the effects of salt reduction were not simultaneously evaluated in a comparator group. As an example, some trials tested the BP effects of salt reduction in patients with diabetes [36], yet none tested the effects concurrently in patients without diabetes. Also, most meta-analyses aggregate published data across studies rather than analyzing individual-level data; such studies are poorly suited to identify subgroups that are SS. By contrast, some studies, such as the DASH-Sodium trial, have simultaneously examined the effects of salt in both sexes, in Black and White patients, by age, and over a broad range of baseline BP [17,18,37].

In aggregate, a strong and consistent body of evidence has documented the following:

●Black individuals have a greater BP response to a change in sodium intake compared with White individuals [17-19]. As an example, in the DASH-Sodium trial, the lower sodium diet reduced systolic pressure by 8 mmHg in African American participants and by 5 mmHg in non-African American participants [17].

●Patients with hypertension have a greater BP reduction in response to a decrease in sodium intake compared with nonhypertensive patients; in addition, the BP response to sodium reduction is substantially greater in patients with medication-resistant hypertension [18,38]. The table (table 1) displays the joint effects of sodium reduction by race (African American and non-African American) and hypertensive status (stage 1 and prehypertension) [18], along with the effects of sodium reduction in patients with resistant hypertension [38].

●Older-aged persons have a greater BP response than younger adults [39]. However, children also experience a decrease in BP from sodium reduction [22].

●The effects of sodium reduction depend upon other dietary factors. The effects of sodium reduction on BP are greater in the setting of a low potassium intake [40] and in the setting of a typical American diet compared with the DASH-style diet (figure 3) [37].

Less consistent evidence suggests that women might be more SS than men and that salt sensitivity may increase with higher weight. Few trials have tested the effects of salt reduction on BP in other ethnic populations [41,42] and in persons with diabetes or chronic kidney disease.

Response to antihypertensive drugs — In addition to its direct effect on BP, lowering the extracellular volume by limiting sodium intake can enhance the response to most antihypertensive drugs, except possibly calcium channel blockers [43]. Sodium reduction may also diminish the degree of potassium depletion following treatment with a diuretic [44].

Dietary sodium reduction, by increasing renin release, makes the BP more dependent upon angiotensin II and, therefore, more responsive to therapy with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB) [45]. A less responsive renin-angiotensin system may be one reason why Black patients appear to be more sensitive to sodium reduction than White patients. Even patients being treated with the combination of a diuretic and an ACE inhibitor benefit from a reduction in sodium intake (eg, from 195 to 105 mEq/day); in this setting, mean BP fell by an average of 9/3 mmHg [45].

Several trials have documented that sodium reduction lowers urinary protein excretion [46]. In patients with proteinuric chronic kidney disease who are already treated with ACE inhibitors, reducing sodium intake substantially decreases both BP and proteinuria to a degree greater than that achieved by addition of an ARB to the ACE inhibitor [43]. (See "Antihypertensive therapy and progression of nondiabetic chronic kidney disease in adults", section on 'Importance of salt intake' and "Overview of hypertension in acute and chronic kidney disease", section on 'Benefits of sodium restriction'.)

Sodium intake does not appear to have an important influence on the degree of BP control achieved by calcium channel blockers [47]. This may be due to natriuresis that occurs after initiation of a calcium channel blocker, similar to that seen with a diuretic [48]. A natriuretic effect of calcium channel blockade may appear surprising in view of the common complication of peripheral edema in patients treated with dihydropyridine calcium channel blockers. However, the edema in this setting results from redistribution of fluid from the vascular space into the interstitium rather than renal sodium retention. (See "Major side effects and safety of calcium channel blockers".)

Effects of sodium on cardiovascular disease — By lowering BP and preventing hypertension, sodium reduction should theoretically reduce cardiovascular disease. Overall, the best available evidence strongly supports population-wide sodium reduction as a means to prevent cardiovascular disease and stroke [49].

Several studies have estimated the public health benefits and cost savings attributable to the BP effects of a reduced sodium intake. In one study, reduction of dietary salt intake by 3 g/day was projected to save 194,000 to 392,000 quality-adjusted life-years and substantially reduce health care costs, while reducing the annual number of deaths by 44,000 to 92,000 [50,51].

Salt substitutes, in which a proportion of sodium chloride is replaced with potassium chloride, have been studied to assess the effects of sodium reduction on cardiovascular outcomes and mortality [27,28,52]. In a meta-analysis of five randomized trials with 24,306 participants, salt substitutes reduced the relative risk of all-cause mortality by 11 percent, cardiovascular mortality by 13 percent, and cardiovascular events by 11 percent [28].

Many observational studies have examined the relationship of sodium intake or sodium excretion with cardiovascular disease, and most found that a high sodium intake increases the risk of cardiovascular disease and death [5,53,54]. In perhaps the strongest evidence of a direct, progressive relationship, a meta-analysis of observational studies documented that higher sodium intake, estimated from multiple 24-hour urine samples, was associated with increased cardiovascular risk in a progressive, dose-response manner without evidence of harm at lower levels of sodium excretion [53]. These data contrast with some observational studies that found increased risk at both high sodium intake and low sodium intake or excretion (ie, a U- or J-shaped relationship was observed) [55,56]. However, such paradoxical findings likely resulted from methodologic limitations, such as the use of a single spot urine collection (rather than multiple 24-hour collections) to estimate an individual's usual sodium intake and the possibility that individuals at high risk for cardiovascular disease choose to reduce their sodium intake (ie, reverse causation) [57].

The assessment of sodium intake is fraught with methodologic challenges [57]. Both systematic and random errors in the measurement of dietary sodium intake are commonplace. The gold standard remains measurement of urinary sodium excretion from multiple high-quality, 24-hour collections, but even these estimates can be inaccurate because of collection problems (most commonly, undercollection). In addition, because of large day-to-day, within-person variation, repeat measurements on multiple days are needed to obtain precise estimates of an individual's usual intake [58,59]. Such variability reflects both high day-to-day variation in sodium intake as well as variation in urinary excretion even on a fixed intake [60].

Other adverse effects of excess sodium — Excess sodium intake has adverse effects apart from its influence on BP [61-63]. A large body of observational evidence as well as one clinical trial [64] link higher sodium intake with higher left ventricular mass [2]. Other intervention studies have documented that sodium reduction improves vascular structure and function [65,66]. In addition, excess sodium intake appears to increase the risk of gastric cancer [67], proteinuria [46], kidney stones, and osteoporosis [68]. The last two disorders reflect the direct relationship of sodium intake with urinary calcium excretion; as sodium intake increases, so does calciuria [69] (see "Kidney stones in adults: Prevention of recurrent kidney stones", section on 'Limit sodium intake'). Two studies have documented that increased sodium intake raises the risk of headaches [70,71], and some evidence has also linked excess sodium intake with altered immunity and the occurrence of autoimmune diseases, such as multiple sclerosis [72].

Hypothesized adverse effects of sodium reduction — There is no evidence that a low sodium intake is a public health problem. Even though extreme sodium reduction to <20 mmol/day might adversely affect insulin resistance and blood lipids, moderate sodium reduction has no such effects [39]. Potential adverse effects of a reduced sodium intake are increases in uric acid and plasma renin activity (PRA). However, the clinical relevance of modest rises in uric acid and PRA as a result of sodium reduction and other antihypertensive therapies is unclear. In fact, thiazide-like diuretics, a class of antihypertensive drug therapies that raises uric acid and PRA, significantly reduce the risk of cardiovascular disease.

CLINICAL RECOMMENDATIONS — A low-salt diet is recommended in all international and national guidelines as a component of nonpharmacologic therapy of primary hypertension (formerly called "essential" hypertension) [73,74].

Major society recommendations — Almost all national and international organizations recommend dietary sodium reduction as part of the nonpharmacologic therapy for hypertension. The following is a sample of prevailing recommendations:

●In 2013, the World Health Organization (WHO) recommended that adults consume <2000 mg/day of sodium.

●The 2020 United States Dietary Guidelines, prepared by the United States Departments of Agriculture and of Health and Human Services, recommend that adults consume ≤2300 mg/day of sodium [75].

●The American Heart Association set 1500 mg/day of sodium as the recommended upper limit of intake for all Americans [7].

●The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend a sodium intake of <2 g (90 mmol)/day for patients with chronic kidney disease not on dialysis [76].

●The Canadian Cardiovascular Harmonized National Guidelines Endeavour (C-CHANGE) guideline recommends reducing sodium intake toward 2 g/day to prevent and treat hypertension for adults [77].

Guidance for health care providers — Clinicians have an important role in promoting lifestyle changes, of which sodium reduction should be a major goal. A brief supportive message on the benefits of sodium reduction, even without extensive counseling, should be beneficial. Still, reducing sodium intake requires behavioral change and skills (eg, identification of higher-sodium foods and substitution with similar foods that are lower in sodium). Accordingly, provision of pamphlets, while useful in identifying foods with high amounts of sodium, is an incomplete approach. Counseling from a skilled dietitian or health educator, coupled with tracking of sodium intake, is often required to accomplish meaningful reductions in sodium intake (table 2) [78]. Among persons whose major source of sodium is salt added during cooking or at the table, replacement of regular salt with potassium-enriched salt is a promising therapy that lowers blood pressure; however, caution is warranted for those who are at risk for hyperkalemia, such as persons with advanced kidney disease [79].

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Low-sodium diet (The Basics)")

●Beyond the Basics topic (see "Patient education: Low-sodium diet (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Effect of sodium on blood pressure – A high dietary intake of sodium is associated with elevated blood pressure (BP) and the development of hypertension. (See 'Effect of sodium on blood pressure' above.)

●Rationale for dietary sodium reduction – Dietary sodium reduction can lower BP in both hypertensive and normotensive individuals, prevent hypertension, and enhance the BP response to most antihypertensive therapies (see 'Scientific rationale for dietary sodium reduction' above and 'Effects of sodium on cardiovascular disease' above). In general, the extent of BP reduction as a result of reduced sodium intake is greater in Black patients, middle- and older-aged persons, individuals with hypertension, and, likely, patients with diabetes or kidney disease. (See 'Variability in the blood pressure response to sodium' above.)

Dietary sodium reduction should decrease the risk of cardiovascular disease through its effects on BP and other effects that are independent of BP. (See 'Effects of sodium on cardiovascular disease' above.)

●Clinical recommendations – In hypertensive individuals, we recommend reducing dietary sodium intake (Grade 1B). A reasonable goal is to reduce daily sodium intake to <100 mEq (2.3 g of sodium or 6 g of sodium chloride)/day. Further reduction to approximately 50 mmol/day has an even greater effect on BP but is difficult to achieve given the prevailing food supply. (See 'Clinical recommendations' above.)

In persons without hypertension, we also suggest reducing dietary sodium intake to the same level (<100 mEq [2.3 g of sodium or 6 g of sodium chloride]/day) with the goal of preventing hypertension and decreasing the risk of stroke and other cardiovascular events (Grade 2B). (See 'Clinical recommendations' above.)