Sodium reduction and salt substitutes: impact on blood pressure and recurrent stroke

Abstract

Purpose of review

The health effects of dietary sodium and dietary potassium intake in mitigating blood pressure (BP) are a focus of research. This review summarizes recent findings of these health effects and the effectiveness of potassium-enriched salt substitutes on the risk for and recurrence of cardiovascular events.

Recent findings

Salt substitution is an emerging sodium reduction strategy that may prove to be more beneficial in lowering BP and reducing risk for recurrent stroke compared with alternative low-sodium diets. However, careful consideration is required for patients with impaired renal function or on specific renal physiology-modulating pharmacotherapies.

Summary

Low sodium substitutes have proven to be more efficacious and practical in lowering BP and preventing stroke or recurrence of stroke than alternative low-sodium diets. This salt reduction strategy holds promising value in reducing the risk for cardiovascular disease.

INTRODUCTION

The physiological link between excessive sodium intake and increased blood pressure (BP) is well established, contributing to a global burden of morbidity and mortality from conditions like stroke [1–10]. While public health campaigns have long advocated for reduced salt consumption, the growing interest in salt substitutes, such as potassium chloride, presents a promising alternative in diverse populations [1,3,4,6]. A driving force behind these efforts is the well documented health benefits of dietary potassium, particularly its role in reducing BP and stroke risk [3,4,11^▪▪]. The present review evaluates the impact of dietary sodium reduction and the use of salt substitutes on BP and the incidence of recurrent stroke. 

Box 1.

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BP AND STROKE

BP is the most prevalent and modifiable risk factor for stroke, with hypertension being reported in approximately 65% of patients with stroke [4–8,12]. In the global InterStroke study, patients with hypertension were twice as likely to experience a stroke compared with normotensive individuals [13]. Small reductions (~5 mmHg) in BP result in substantial reductions in risk for cardiovascular events [4]. Generally, 25% of strokes are recurrent with a mortality rate of 41% [5]. This necessitates appropriate BP control to reduce the risk of a recurrent event [12,13]. In Finland, the salt intake reduction collaboration initiated in the 1970s resulted in a decrease of >10 mmHg in both systolic and diastolic BP and a 75–80% reduction of stroke and coronary heart disease mortality, which increased life expectancy by 5–6 years [6].

DIETARY SODIUM AND BP

Many studies show that decreased sodium consumption is associated with reduced BP and cardiovascular events [1,3,6,14]. Moreover, there is a dose-dependent relationship: the greater the reduction in dietary salt, the bigger the decrease in systolic BP. A sodium reduction of 3 g daily is estimated to reduce annual cardiovascular mortality by 50% [2,4]. A study in China showed that dietary salt reduction could prevent between 183 000 and 540 000 new cases of cardiovascular disease annually [15]. Furthermore, dietary sodium intake regulates BP early in life and exerts long-term health effects. In a study of 476 infants, feeding them a low-sodium formula during the first 6 months of life resulted in a significantly lower systolic BP (i.e., 2.1 mmHg) compared with those fed normal formula [6]. Fifteen years later, the difference in systolic BP increased to 3.6 mmHg, suggesting that the protective effects of a low-sodium diet are long lasting.

A standard method of reducing dietary sodium intake is to consume a healthy diet. In the Dietary Approaches to Stop Hypertension (DASH) trial, participants who consumed a diet: rich in fruits, vegetables, and low-fat dairy products, and, low in sodium, saturated fat, added sugars, and cholesterol had lower systolic and diastolic BP than patients eating a regular diet [10,16^▪▪,17]. The subsequent DASH-Sodium trial evaluated the impact on BP of sodium reduction alone and combined with the DASH diet [2]. The combination of DASH diet and low sodium resulted in the greatest decrease in 10-year atherosclerotic cardiovascular disease (ASCVD) [6,9,10,17–19,20^▪]. Compared with high sodium intake, low sodium intake reduced ASCVD risk by 9.4%. Compared with a typical American diet, the DASH diet reduced 10-year ASCVD by 5.3%. Compared with a high sodium-control diet, the combination of both low sodium intake with DASH lowered ASCVD risk by 14.1% [20^▪]. Accordingly, the World Health Organization (WHO) has deemed population-wide salt reduction interventions to be a cost-effective, feasible global approach for hypertension prevention and control [14].

PATHOPHYSIOLOGY OF EXCESS SODIUM INTAKE

The quantity of sodium required to maintain cellular homeostasis in adults is <1.25 g daily [3,21]. However, modern diets include salt in larger quantities than required for homeostasis [3,22]. Excessive salt intake leads to water retention, increased systemic peripheral resistance, changes in endothelial function, altered structure and function of large elastic arteries, changes in sympathetic output, and disruptions in the autonomic neuronal modulation of the cardiovascular system [21–23]. These changes may increase BP via several mechanisms, including [2,3,21] increased extracellular volume, activation of the renin-angiotensin aldosterone system (RAAS), induction of transforming growth factor-β with increased arterial wall extracellular matrix and compliance [10,23], and reduction in bioavailability of nitric oxide (NO), which is necessary for vasodilation [10,23].

DIETARY SODIUM AND RESTRICTION

The most accurate assessment of dietary sodium and potassium consumption is the urinary sodium:potassium ratio, [24–27] with a ratio <1 the recommended target for improving long-term BP control. This can be accomplished by restricting sodium intake, increasing potassium intake, or both [1,26]. Globally, consumption of sodium is double that of the recommended 2 g/day and consumption of potassium is half that of the daily recommended 3510 mg/day [25,26,28,29^▪▪,30^▪▪,31].

Sodium is highly prevalent in our food choices [1,21]. Seventy percentage of sodium in the average diet comes from processed foods, and the main contributors of sodium in the U.S. diet are store-bought foods at 61% and restaurants at 29% [3,30^▪▪]. Globally, the highest contributions of sodium in diet are bread and baked goods, cereals and grains, and meat and dairy products [4].

Despite the proven benefit of sodium restriction, sodium intake has largely remained unaltered over the past decades [3,4,6,7,28]. Less than half of patients follow their prescribed sodium restriction diet [4,21]. From 1999 to 2016, adherence to the U.S. Department of Agriculture sodium intake guidelines decreased from 34% to 23%, with <10% adherence in high-risk subgroups [4]. Numerous reasons contribute to difficulty in following a low-sodium diet, including cost and food choice limitations, loss of taste, and confusion when patients with co-morbidities are asked to follow more than one type of diet [21]. Socioeconomic status also adversely affects compliance with reduced sodium intake, with individuals in a lower socioeconomic position having a 5–10% higher salt intake than those in higher positions [4].

To determine if salt substitutes can maintain the flavor profile of normal salt, Consumer Reports conducted a blind taste test of salt substitutes. Tasters found that combinations of sodium and potassium chloride tasted and looked like the salt they were used to consuming, with no ability to discern the difference in rice and eggs seasoned with the salt substitutes [4]. Thus, legislation to gradually reduce the amount of salt the food industry adds to foods may show promise in creating a sustainable reduction in population sodium intake [7].

SODIUM SUBSTITUTES

An inverse relationship exists between sodium and potassium in foods, with those high in sodium being lower in potassium [28]. Thus, diets that are low in sodium are often rich in potassium [28]. Underconsumption of potassium, particularly when combined with high sodium intake, has been associated with a variety of chronic disorders, including hypertension, diabetes, obesity, and renal calculi [3,16^▪▪,28]. Because sodium is essential in maintaining physiologic homeostasis, controversy exists regarding how large the reduction in salt intake should be. Consequently, potassium-enriched salt replacement therapy has been proposed as an alternative salt reduction strategy [3,4,30^▪▪,32]. Potassium-enriched salt substitutes are made by replacing a proportion of the sodium chloride in regular salt with potassium chloride, effectively increasing dietary potassium intake while decreasing dietary sodium intake [32].

POTASSIUM INTAKE AND BP

Potassium can affect BP by exerting natriuretic effects on the kidney, vasoactive effects on the vasculature, and decreased sympathetic outflow [4,10,16^▪▪,23,26,33,34].

The natriuretic effect of increased dietary potassium intake occurs through the coordinated actions along multiple nephron segments. An inhibitory effect on proximal tubular sodium transport in response to potassium loading has been attributed to slight increases in extracellular potassium concentration causing inhibition of the apical sodium-hydrogen exchanger (NHE3) [4,35]. Changes in membrane potential leads to intracellular alkalinization resulting in reduced sodium and bicarbonate reabsorption. Increased potassium intake also inhibits sodium reabsorption in the thick ascending limb by exerting a depolarizing effect that results in inhibition of the sodium-potassium-chloride cotransporter [4].

Because the proximal tubule and thick ascending limb are high-capacity segments responsible for reabsorbing most of the filtered sodium, these segments lack the precision required to ensure that downstream delivery is appropriate to maximally stimulate potassium secretion without becoming excessive and predisposing to volume depletion [4]. For this reason, the low-capacity nature of the distal convoluted tubule is the critical site of potassium-induced natriuresis. Increased extracellular potassium depolarizes the basolateral membrane of distal convoluted tubule cells, raises intracellular chloride concentration, which inhibits WNK kinases (with-no-lysine kinases), which ultimately reduces activity of the sodium-chloride cotransporter [4]. This coordinated response promotes simultaneous natriuresis and kaliuresis, facilitating potassium excretion while preventing sodium retention and extracellular volume expansion [26,34,36].

Potassium also exerts direct vasodilatory effects on vascular smooth muscle [34]. Potassium can improve arterial stiffness by inhibiting free radical formation in vascular endothelial cells and macrophages, vascular smooth muscle cell proliferation, platelet aggregation, and arterial thrombosis [23,33].

POTASSIUM INTAKE AND STROKE

Maintenance of potassium homeostasis in the body is important for reducing the risk of cardiovascular disease [36]. Higher potassium intake is associated with lower BP and risk of stroke, with a study showing women taking >3100 mg of potassium daily had a 16% lower risk of ischemic stroke as opposed to women taking <1925 mg [37,38]. However, increasing potassium intake without reducing sodium only has a modest effect on BP [26,29^▪▪,37]. Thus, potassium-enriched salt substitutes have been proposed as an alternative to normal salt [4,40], thus increasing potassium intake to reduce sodium intake [3].

A common salt substitute combination is 75% sodium chloride:25% potassium chloride [3,6,32,41^▪,42]. The Salt Substitute and Stroke Study (SSaSS) conducted in northern China evaluated the effects of a salt substitute against regular salt on recurrent stroke and mortality among patients with stroke [41^▪]. Salt substitute was significantly more protective against recurrent stroke and death rate than regular salt [41^▪]. In Peru, a cluster randomized trial found modest improvements in systolic BP in individuals who used a salt substitute [6,42]. In India, a randomized controlled trial found that salt substitution led to significant reduction in systolic BP compared with normal salt [3]. Further, a national modelling study in China estimated that the use of potassium-enriched salt substitutes would prevent 461,000 deaths due to cardiovascular disease annually (i.e., an 11% reduction) [43]. These studies demonstrate that the beneficial effects of salt substitutes on BP and cardiovascular disease can be generalized across populations globally [44].

Salt substitution strategies have been compared with alternative salt reduction methods in China. A meta-analysis in China comparing four salt reduction strategies showed that salt substitution was an effective strategy in mitigating BP levels [14,45]. A systematic review comparing the dietary strategies of energy deficit, Mediterranean-like diet, and salt substitution showed modest, significant reductions in cardiovascular events, whereas salt reduction, the DASH diet, and alcohol reduction showed small reductions in BP, but no reduction in cardiovascular events [46]. There is also evidence for a combined strategy of using salt substitutes in combination with the low-sodium DASH diet. In older patients with hypertension and type 2 diabetes this combination led to a significant reduction in systolic and diastolic BP (i.e., 14.3 mmHg and 6.3 mmHg from baseline, respectively) compared with DASH diet alone [23]. Finally, a long-term study found that salt substitutes can significantly reduce cardiovascular disease and overall stroke mortality in hypertensive patients [23]. Overall, these studies show that a salt substitute strategy may be a superior method to salt reduction [3].

SAFETY OF POTASSIUM INTAKE

Hyperkalemia is uncommon in individuals with normal renal function [6]. Accordingly, in a population of stroke patients, SSaSS found no increased adverse hyperkalemic events in the salt substitute versus the normal salt groups [41^▪]. However, in patients with stage 3 or 4 chronic kidney disease or patients taking a potassium-sparing diuretic, there is strong concern for hyperkalemia Additionally, chronic kidney disease patients are typically treated with medications that raise plasma potassium concentration. Combining a potassium-enriched diet with RAAS inhibitors can cause hyperkalemia in this patient population [4,6,28,39,47,48,49–51^▪].

Administration of salt substitutes to the general population may raise concerns of hyperkalemia and death in individuals with undiagnosed chronic kidney disease. However, a modeling study of the impact of a potassium-enriched salt substitute in the general population showed that despite any unintended increase in mortality due to hyperkalemia in the occasional individual with unsuspected chronic kidney disease, there would be an overall net mortality benefit due to a reduction in cardiovascular deaths [6]. Hence, there may be an overall benefit of using a salt substitute in the entire population, but this warrants further investigation [48].

FUTURE DIRECTIONS

In the U.S., much of the population's dietary sodium is derived from purchased, processed foods. However, in China most of the population's dietary sodium is derived from meals prepared at home. This shows that the root cause of sodium overconsumption may vary by population. Thus, when developing a strategy for reduced salt intake, it is important to understand the target demographic. Further high-quality trials in diverse populations with varying socioeconomic status, cultural behavior, and health status may better guide interventions. Additionally, future directions may include studies on optimal sodium:potassium chloride ratios in salt substitutes.

CONCLUSION

Low-sodium substitutes have proven to be more efficacious and practical in lowering BP and preventing stroke or recurrence of stroke than alternative low-sodium diets. Additionally, their use in the general population appears to be safe. This low-cost salt reduction strategy holds promising value in reducing the risk for cardiovascular disease worldwide.

Acknowledgements

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Financial support and sponsorship

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Conflicts of interest

The authors have no relevant financial disclosures or conflict of interests.

REFERENCES AND RECOMMENDED READING

Papers of particular interest, published within the annual period of review, have been highlighted as:

• ▪ of special interest

• ▪▪ of outstanding interest