Dietary sodium reduction is best for reducing blood pressure: Controversies in Hypertension

Abstract

The global burden of cardiovascular disease (CVD) continues to grow, as does the incidence of hypertension, one of the most important modifiable risk factors of CVD. Non-pharmacologic, population level interventions are critically needed to halt the hypertension pandemic, but there is an ongoing debate as to whether public policy efforts should focus more on dietary sodium reduction or increasing potassium. In this commentary, we summarize arguments in favor of policy geared towards reduced sodium intake. Recognizing increasing dietary sodium as one of the drivers of the hypertension pandemic is critical to developing public policy to reduce population level sodium exposure and blood pressure. We draw from a robust field of evidence to show that reducing sodium intake improves blood pressure in a linear fashion, across the lifespan, at an individual level and a population level, and may even reduce CVD events. While potassium plays an important role in blood pressure regulation, potassium interventions are less effective at reducing blood pressure, carry risk of hyperkalemia in select populations, and are more logistically challenging. There is an urgent need for nation-wide policies to reduce sodium intake to help stem the hypertension pandemic and prevent CVD.

Introduction:

Cardiovascular disease (CVD) remains the primary cause of death worldwide and the burden of CVD is rising.¹ While multiple factors are implicated in these trends (e.g., obesity), the sodium content in processed foods has steadily increased and is viewed as a major cause of CVD-related morbidity and mortality worldwide due to its contribution to hypertension.² It is estimated that over 1.3 billion people have hypertension,³ one of the most important, modifiable risk factors for CVD.¹ In 2010, 9.5% of deaths from cardiovascular disease worldwide, were attributed to increased sodium consumption above a reference level of 2.0 g/day, amounting to 1.65 million deaths in total.⁴ Recognizing the role of sodium in the global hypertension pandemic, is essential for the development of public policies that can reduce sodium exposure at the population level.

Both the United States Department of Agriculture (USDA) and the World Health Organization (WHO) recommend lower sodium diets. However, adherence to these recommendations is suboptimal. Median sodium consumption among 47,509 Americans between 1999–2016 increased from 3156 mg/day to 3273 mg/day. Moreover, adherence to USDA intake guidelines over this time period decreased from 34% to 23%, with less than 10% adherence in high risk subgroups.⁵ Similarly, the WHO recommendation for sodium intake is about 2 g/day.⁶ However, in 2010 the mean global sodium intake was 3.95 g/day, with the highest intakes in East Asia, Central Asia, and Eastern Europe where mean intake was over 4.2 g day.⁷ As of 2023, only 9 countries met WHO recommendations for policies to reduce sodium intake at the population level.⁸

In this debate, we present a rationale for why sodium reduction is central to effective public policy to reduce hypertension and prevent CVD. While other approaches, such as promoting increased potassium intake, are helpful, they are reactive to excess sodium intake and cannot stem the rise in hypertension and CVD events alone without addressing the primary driver of these chronic, debilitating, and preventable conditions.

Why sodium

Sodium and Blood Pressure

There are few nutrients with as much experimental evidence in support of a direct, causal relationship with a CVD risk factor, as sodium and blood pressure (BP). In the seminal DASH-Sodium trial, 412 participants were assigned to eat a high, intermediate, and low sodium diet for 30 days each, in random order, as part of a healthy diet (the DASH diet) or a typical American diet (which targeted the 25^th percentile for intake of potassium and other nutrients). The authors demonstrated a dose-dependent effect of sodium reduction on BP regardless of diet. The largest reduction in systolic BP, −6.7 mm Hg, was observed when sodium intake was lowered from high (150 mmol/day) to low (<50 mmol/day) intake levels. ⁴

In a meta-analysis of 85 trials and >10,000 participants, Filippini and colleagues demonstrated a consistent, linear relationship between sodium and BP, regardless of baseline sodium exposure or BP.⁹ This stands in contrast to micronutrients like potassium, that in a meta-analysis of 32 trials, exhibited a U-shaped relationship with BP, and did not seem to lower BP in the context of a lower sodium diet.¹⁰

Sodium and cardiovascular disease

There is evidence linking sodium directly with CVD prevention. NT-proBNP is a strong predictor of CVD events,^11,12 that is lowered in response to hypertension treatment.¹³ An observational study of 1,404 healthy participants, found that those with the highest dietary sodium intake (>9.62g/day) had the highest BNP levels (14.70 pg/mL), nearly double the levels of those in the lowest sodium intake group.¹⁴ Moreover, in the DASH-Sodium trial, only sodium reduction lowered NT-proBNP, while the potassium-rich DASH diet had no impact on NT-proBNP.¹⁵ These findings suggest that sodium intake is directly linked to downstream sequelae of hypertension and known injury pathways for CVD.

In addition, post-hoc analyses of trials of sodium intake suggest that sodium intake is directly linked with CVD events. The Trial of Hypertension Prevention I, conducted in 2,182 healthy participants, showed that sodium reduction lowered systolic BP by 1.7 mm Hg, while supplementation of potassium at a level achievable with dietary intake, demonstrated no significant changes on BP.¹⁶ A subsequent observational analysis of extended follow-up after the trial, demonstrated a direct linear relationship between sodium intake and mortality rate over a period of 26 years with higher risk of mortality at high sodium intake and no evidence of a U- or J-shaped relationship.¹⁷

Benefits from sodium reduction across the lifespan

The profound effect that sodium exerts on human physiology begins early in life and appears to be long-lasting. A randomized trial of 476 infants showed that those with lower sodium formula during the first 6 months of life had a significantly lower systolic BP (2.1 mmHg) when compared to those with normal sodium formula.¹⁸ In an observational extension study of this trial, differences in systolic BP increased to 3.6 mmHg by 15 years, suggesting that early sodium exposure had a significant effect on long-term cardiovascular health.¹⁹ Benefits from sodium reduction are also observed at later stages of life. In the TONE study, 975 adults aged 60 years and older with hypertension, assigned to sodium reduction compared to usual care, had a lower risk of high BP antihypertensive medications, or cardiovascular disease events over 36 months of follow-up.²⁰

Population-level evidence

At the population-level, there is strong evidence that sodium reduction lowers BP and potentially cardiovascular disease. In 1989, Fort et al. conducted a trial in two similar villages in Portugal. One village was requested to lower salt intake by half while the other village continued with the same amount of salt intake and served as the control group. After 2 years, the authors reported a difference of 13 and 6 mm Hg in the systolic and diastolic BP, respectively, across groups.²¹ Similar benefits of sodium reduction have been observed in Japan and Finland after nationwide sodium reduction programs were implemented. In Japan, in the late 1950s, a government campaign to lower the incidence of stroke by decreasing the average salt intake resulted in a decrease in average BP in both adults and children, as well as an 80% reduction in stroke mortality.²² In Finland, the salt intake reduction collaboration, started in the 1970s, resulted in a decrease of over 10 mm Hg in both average systolic and diastolic BP as well as a 75–80% reduction of stroke and coronary heart disease mortality. The profound BP reduction from this initiative was believed to increase life expectancy by 5–6 years.²³ Average daily sodium intake in both of these countries is much greater than in other comparable high income countries like the United States (US), so further studies are need to assess the efficacy of this strategy in the US population.

Sodium substitution trials

A more recent population-level intervention trial, the Salt Substitute and Stroke Study (SSaSS), demonstrated the efficacy of substituting table salt with potassium salt to reduce the risk of stroke, major cardiovascular events, and death.²⁴ This prospective, open-label, cluster randomized control trial involved 20,995 participants (age ≥60 years with hypertension) in 600 villages across rural China, testing the effect of sodium reduction education and table salt substitution with a potassium salt substitute, containing 25% potassium chloride. Participants were followed for 5 years and the study found a decrease of 8% in urine sodium excretion and an increase of 56% in urine potassium excretion in the experimental group compared with the control group. There was an accompanying reduction in BP of −3.3/−0.7 mmHg, and significant reductions in the rate of stroke, major cardiovascular events, and death in the experimental group compared with the control group.

While the education component of SSaSS’s intervention focused on salt reduction, the increase in urine potassium in the experimental group and only partial replacement of sodium is often cited as evidence that potassium was the driver of the BP effects in SSaSS.²⁵ However, there are important limitations to single 24-hr urines for estimating sodium intake.²⁶ Moreover, a recent meta-analysis of salt substitution demonstrated no difference in effect on BP between substitutes that used less than 30% potassium chloride compared to over 30% potassium chloride substitutes, questioning the relative importance of potassium compared with reduced sodium intake.²⁷ A prior meta-analysis evaluating the relationship between potassium and BP showed that potassium supplementation primarily reduced BP in the setting of low potassium intake and high sodium intake,¹⁰ which are conditions that exist in rural China (where the SsaSS trial was conducted). This raises questions about the generalizability to other settings where potassium intake is higher and sodium intake is lower. This finding may explain results from phase 1 of the TOHP trial, which found sodium reduction to be a superior strategy for BP reduction than potassium supplementation in a head-to-head comparison.¹⁶ Finally, a study evaluating the efficacy of the DASH diet in a population with hypertension and metabolic syndrome found that the reduction in BP effects could not be accounted for by greater potassium intake provided by the diet.²⁸

Behavioral rationale to address sodium

Commercial incentives have been a major driver of the rise in sodium consumption globally, driven in part by behavioral effects of excess sodium intake. One important downstream effect of high salt intake, is suppression of sodium receptors, resulting in gradual conditioning and increased cravings for high sodium foods.²² This process may take as much as 3 months to reverse.²⁹ Moreover, multiple studies have demonstrated adaptation with sodium restriction, such that sodium restriction enhances recognition of salty taste.^30–32 Finally, excess sodium intake causes increased thirst,³³ which could lead to increased consumption of unhealthy beverages, contributing to related adverse health outcomes.²² Thus, targeting sodium reduction could have direct benefits on lifestyle behaviors beyond salt and BP.

Obstacles facing a policy focus on potassium

While potassium intake should be increased to improve BP, there are a number of pragmatic challenges related to implementing this as a strategy to prevent hypertension.^34,35 Whereas sodium public policy focuses on addressing a human-made problem of high exposure (from processed foods or excess personal seasoning), potassium strategies focus on increasing population-wide intake of potassium. On the individual level, this entails supplementation, potassium salt substitutes, or dietary changes. On the population level, strategies include industry-level potassium salt substitutes or potassium fortification.

While in populations with normal kidney function there has been no evidence to suggest an increased risk from potassium,³⁶ this has not been assessed in populations with kidney disease or taking potassium sparing diuretics. Given the emphasis on increasing potassium intake, there is a greater burden to avoid harms associated with hyperkalemia. Notably the SSaSS trial excluded individuals using potassium supplements, potassium-sparing diuretics, and adults with “serious kidney disease.”²⁴ In the CKDK crossover trial of 29 adults with an estimated GFR of 30–59 mL/min per 1.73 m², a higher potassium diet of 100 mmol/d versus 40 mmol/day, modestly increased serum potassium and was associated with more hyperkalemic events.³⁷ Hyperkalemia is common in the U.S., affecting 2–3% of Medicare patients and 9% of Medicare patients with chronic kidney disease or heart failure,³⁸ suggesting that this may be an important consideration for implementation of policies focused on potassium.

Feasibility of dietary approaches

Dietary modification to increase potassium intake has been broadly recommended; however, studies have questioned the feasibility of this approach. A cross-national study in 2015 investigated adherence to the World Health Organizations’ recommended high potassium diet (for those without renal disease). It revealed that 80.4% of the populations examined were unable to achieve the listed potassium goal of 3510 mg daily, highlighting that developed countries cannot meet guideline recommendations. As many sources of potassium are already frequently consumed, including milk, coffee, meats, and potatoes, achieving even higher serum potassium levels would likely require a greater emphasis on alternative potassium-rich foods such as beans, fish, and dark-green vegetables.³⁹ In the U.S., it was found that increasing the current average intake of potassium (2800 milligrams per day) to 3500 mg daily would cost an individual approximately $380.⁴⁰ Beyond the financial burden and dietary transition required to adopt this change, access to these foods, perishability, and sustainability are all additional barriers. Finally, per the 1997 DASH diet clinical trial, the focus of dietary modification should be on optimizing many nutrients rather than just one agent.⁴¹

Potassium as a salt substitute

Substituting salt with potassium represents the potassium strategy with the strongest evidence for the prevention of CVD events. In addition to the SSaSS trial described above,²⁴ a study performed in Peru in 2020 implemented a stepped-wedge cluster randomized trial, using a similar salt substitute (75% NaCl and 25% KCl) and found modest improvements in systolic BPs.⁴² Despite finding a significant increase in urinary potassium and minimal change in urine sodium, these results should be interpreted with caution given that the authors did not report information regarding baseline dietary intake of sodium or potassium. As discussed above, the effects of potassium independent of sodium intake remain unknown. In addition, like SSaSS, those with kidney disease were excluded, which limits generalizability. Additional barriers to salt substitutes include the likelihood of transitioning away from familiar table salt, adherence to the new salt product, and implementation among populations where most of the sodium is added within homes while cooking (e.g., China) versus outside of the home by industry (e.g., Japan, U.K., or U.S.).⁴³

Potassium supplementation and fortification

There are challenges with implementing potassium supplementation and fortification that should be considered. Potassium supplements can be bitter and fortifying foods with potassium may affect their palatability.⁴⁴ While multiple trials have reported BP reduction from potassium supplementation, a Cochrane review of 6, more rigorous clinical trials with reduced risk of bias that compared potassium supplementation to control, found no statistical difference between study arms.⁴⁵ Furthermore, the supplement industry is not tightly regulated and supplementation would entail similar compliance challenges (i.e., access, costs, and behavioral adherence) as prescribed medications. Dietary fortification during industrial food processing could resolve some of these adherence concerns, but would still have implications for palatability and hyperkalemia risks. In addition, potassium-containing salts are more expensive than sodium chloride. For example, in the SSaSS trial, the potassium chloride substitute used was 1.5 times the cost of regular table salt,²⁴ which represents another barrier to implementation, as this could reduce manufacturing profits or pass additional costs on to consumers, which might be prohibitive for lower income earners. Finally, an important implication of the original DASH trial was that nutrients in supplements likely would not result in the same BP reduction as nutrients in food due to possible interactions or altered bioavailability.

Conclusion

There is no doubt that lower BP reduces CVD and mortality. Public health initiatives are needed for effective primary prevention of hypertension and CVD. Despite a well-known association between high sodium intake and hypertension and robust data suggesting the benefits of sodium reduction, adherence to established recommendations remains poor. Policy that regulates industry practices of adding excess sodium to the population-wide food supply, should be considered as a critical step to overcome the growing epidemic of high salt intake and hypertension, especially in nations where there is high consumption of processed foods. Indeed a recent US Food and Drug Association proposal to allow the use of salt substitutes in prepared foods to reduce sodium, is a promising development. In countries with high sodium consumption from home cooking, such as China, a different strategy may be needed which emphasizes education and table salt substitution to promote changes in behavior. While potassium plays an important role in BP regulation, potassium interventions are less effective for BP reduction, depend on contextual high sodium or low potassium intake, and raise concerns about risk of hyperkalemia in select populations. Moreover, population-wide strategies to promote potassium intake through diet are logistically challenging, while supplementation or fortification lack efficacy and safety data. Consistent with recent calls by the WHO, nation-wide sodium reduction policies remain central to stemming the world-wide hypertension pandemic to prevent CVD.

Abbreviations:

CVD

cardiovascular disease

USDA

United States Department of Agriculture

WHO

World Health Organization

DASH

Dietary Approaches to Stop Hypertension

BP

blood pressure

SSaSS

Salt Substitute and Stroke Study