Objectives:

This systematic review synthesized the evidence regarding the effects of interventions to decrease sodium intake or increase potassium intake on cardiovascular and renal disease outcomes and related risk factors, as well as evidence from prospective cohort studies on the associations between sodium, potassium, or sodium to potassium ratio and these outcomes. The purpose of the review is to provide a future Dietary Reference Intakes (DRI) Committee with the evidence on chronic disease endpoints for consideration in reviewing the DRIs for sodium and potassium.

Data sources:

PubMed®, Embase®, the Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, CINAHL®, Web of Science, references of prior reviews, hand searches of gray literature, and expert recommendations.

Review methods:

Two reviewers independently screened citations and full-text publications. Eligible studies included randomized controlled trials (RCTs), nonrandomized controlled trials, and prospective observational studies published through 2017 that enrolled healthy populations or those with pre-existing hypertension, cardiovascular disease (CVD), diabetes, or obesity and that assessed blood pressure (BP), incident hypertension, achievement of prespecified blood pressure goals, all-cause mortality, CVD morbidity and mortality, coronary heart disease morbidity and mortality, stroke, myocardial infarction, renal morbidity and mortality, kidney stones, and adverse events. We extracted data, assessed risk of bias (RoB, or study quality), summarized and synthesized results, and evaluated the strength of the evidence (SoE) supporting the conclusions separately for conclusions based on controlled trials and those based on prospective cohort studies.

Results:

We identified 15,912 unique citations, of which 257 publications reporting on 171 studies were deemed eligible for the review.

Moderate-strength evidence from 48 RCTs supports a significant BP-lowering effect of dietary sodium reduction in adults (e.g., a decrease of 3.23 mm Hg [95% confidence interval 2.41 to 4.06] in systolic blood pressure with a 42 mmol weighted mean decrease in sodium intake), but sodium reduction interventions do not appear to show statistically significant effects on BP in children (low SoE). Comparing the findings of studies of adults with hypertension with those in adults with normal BP showed that sodium reduction has a greater BP-lowering effect in adults with hypertension than in normotensive adults (moderate SoE). Sodium reduction may also increase the proportion of study participants who achieve a prespecified BP goal (low SoE), but the evidence is unclear regarding the effect of reducing sodium intake on the incidence of hypertension (because of the small number of trials). Prospective cohort studies suggest an association between lower urinary sodium excretion and reduced risk for hypertension (low SoE because of high RoB and lack of consistency).

Only a small number of RCTs assessed the effects of sodium reduction on longer term chronic disease outcomes: Sodium reduction decreased the risk for the combined outcome of CVD mortality/morbidity and a composite outcome of any CVD events (low SoE). Although sodium levels appear to be associated with all-cause mortality (low SoE), the shape of this relationship could not be determined (insufficient SoE), and evidence from prospective cohort studies was insufficient to draw conclusions regarding associations with combined CVD morbidity/mortality and stroke risk.

Use of potassium salt substitutes in place of sodium chloride and increasing potassium intake itself through the use of supplements significantly decrease BP (moderate SoE), but evidence is insufficient to assess their effect on risk for hypertension, kidney stones, or longer term outcomes, including all-cause mortality or CVD, stroke, or renal morbidity or mortality, or the potential moderating effects of other factors, and whether these effects are moderated by changes in sodium intake. Evidence from prospective cohort studies suggests potassium intake may be associated with decreased risk for kidney stones but is insufficient to assess associations of potassium intake with other outcomes of interest.

Conclusions:

Reducing sodium intake, increasing potassium intake, and use of potassium-containing salt substitutes in the diet significantly decrease BP, particularly among those with hypertension. Limited evidence also suggests that sodium intake is associated with risk for all-cause mortality, and that reducing sodium intake may decrease the risk for CVD morbidity and mortality.