Blood Pressure Effects of Sodium Reduction: Dose-Response Meta-Analysis of Experimental Studies

Abstract

Background: The relationship between dietary sodium intake and blood pressure (BP) has been tested in clinical trials and nonexperimental human studies, indicating a direct association. The exact shape of the dose-response relationship has been difficult to assess in clinical trials because of the lack of random-effects dose-response statistical models that can include 2-arm comparisons.

Methods: After performing a comprehensive literature search for experimental studies that investigated the BP effects of changes in dietary sodium intake, we conducted a dose-response meta-analysis using the new 1-stage cubic spline mixed-effects model. We included trials with at least 4 weeks of follow-up; 24-hour urinary sodium excretion measurements; sodium manipulation through dietary change or supplementation, or both; and measurements of systolic and diastolic BP at the beginning and end of treatment.

Results: We identified 85 eligible trials with sodium intake ranging from 0.4 to 7.6 g/d and follow-up from 4 weeks to 36 months. The trials were conducted in participants with hypertension (n=65), without hypertension (n=11), or a combination (n=9). Overall, the pooled data were compatible with an approximately linear relationship between achieved sodium intake and mean systolic as well as diastolic BP, with no indication of a flattening of the curve at either the lowest or highest levels of sodium exposure. Results were similar for participants with or without hypertension, but the former group showed a steeper decrease in BP after sodium reduction. Intervention duration (≥12 weeks versus 4 to 11 weeks), type of study design (parallel or crossover), use of antihypertensive medication, and participants' sex had little influence on the BP effects of sodium reduction. Additional analyses based on the BP effect of difference in sodium exposure between study arms at the end of the trial confirmed the results on the basis of achieved sodium intake.

Conclusions: In this dose-response analysis of sodium reduction in clinical trials, we identified an approximately linear relationship between sodium intake and reduction in both systolic and diastolic BP across the entire range of dietary sodium exposure. Although this occurred independently of baseline BP, the effect of sodium reduction on level of BP was more pronounced in participants with a higher BP level.

Keywords: blood pressure; diet; hypertension; meta-analysis; public health; sodium; systematic review.

Figure 1.

Flow chart of systematic literature search for trials, published through October 12, 2020, that met the study inclusion and exclusion criteria.

Figure 2.

Dose–response meta-analysis of changes in SBP and DBP levels (mm  Hg) according to achieved sodium excretion in the treatment and control groups at the end of the trials (all studies) and by type of intervention (supplementation or diet). The average curve (solid line) with 95% confidence limits (dashed lines) was estimated with a 1-stage random-effects restricted cubic spline model, using 2 g/d as referent. DBP indicates diastolic blood pressure; and SBP, systolic blood pressure.

Figure 3.

Dose–response meta-analysis of changes in SBP and DBP levels (mm  Hg) according to achieved sodium excretion in the treatment and control groups at the end of the trials divided by hypertension status (no hypertension and hypertension). The average curve (solid line) with 95% confidence limits (dashed lines) was estimated with a 1-stage random-effects restricted cubic spline model, using 2 g/d as referent. DBP indicates diastolic blood pressure; and SBP, systolic blood pressure.

Figure 4.

Dose–response meta-analysis of changes in SBP and DBP levels (mm  Hg) according to achieved sodium excretion in the treatment and control groups at the end of the trials stratified by trial duration (4–11 weeks or ≥12 weeks). The average curve (solid line) with 95% confidence limits (dashed lines) was estimated with a 1-stage random-effects restricted cubic spline model, using 2 g/d as referent. DBP indicates diastolic blood pressure; and SBP, systolic blood pressure.

Figure 5.

Dose –response meta-analysis of changes in SBP and DBP levels (mm  Hg) according to the difference in sodium excretion between the treatment and the control groups at the end of the trials (all studies) and by type of intervention (supplementation or diet). The average curve (solid line) with 95% confidence limits (dashed lines) was estimated with a 1-stage random-effects restricted cubic spline model. DBP indicates diastolic blood pressure; and SBP, systolic blood pressure.

Figure 6.

Dose –response meta-analysis of changes in SBP and DBP levels (mm  Hg) according to the difference in sodium excretion between the treatment and the control groups at the end of the trials divided by hypertension status (no hypertension and hypertension ). The average curve (solid line) with 95% confidence limits (dashed lines) was estimated with a 1-stage random-effects restricted cubic spline model. DBP indicates diastolic blood pressure; and SBP, systolic blood pressure.