Nearly linear relationship between sodium intake and BP in individuals with and without hypertension

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

Literature - Filippini T, Malavolti M, Whelton PK, et al. - Circulation. 2021 Feb 15. doi: 10.1161/CIRCULATIONAHA.120.050371.

Introduction and methods

There has been a general acceptance of the association of sodium intake and elevated blood pressure (BP), but some challenge the effectiveness of reduced dietary sodium for BP lowering in individuals without hypertension, and for DBP [1-3].

To date, the exact shape of the dose-response association curve between BP and the entire range of sodium intake is not well known yet, because of heterogeneity across studies. This is due to a lack of flexible models that are capable of including studies with less than 3 comparisons, like 2-arm RCTs [1]. A novel 1-stage or mixed-effects model has recently become available, in which studies with a single comparison can be included in the estimation of heterogeneous and possibly curvilinear dose-response relationships [4,5].

This study conducted a comprehensive dose-response meta-analysis of clinical trials that had investigated the effect of dietary sodium intake on BP over a wide range of sodium exposures using the novel 1 stage cubic spline mixed-effects model.

Trials that were included had 1) at least 4 weeks of follow-up; 2) 24-hour urinary sodium excretion measurements; 3) sodium intervention through dietary modification or sodium reduction followed by supplementation by sodium or placebo; 4) participants with or without hypertension, 5) SBP and DBP measurements before and after the intervention, 6) comparator being normal/high sodium or placebo treatment comparison, without mixed intervention components . In total, 85 trials were included, that had a sodium intake range from 0.4-7.6 g/day. Data from participants with hypertension (n=65), without hypertension (n=11), or a combination of both (n=9) were pooled and assessed for the effect of achieved sodium intake on SBP and DBP levels. As a reference value, 87 mmol/day sodium intake was used, which corresponds to the defined safe intake of 2 g sodium per day or 5 g salt per day [6]. Participants were stratified to sodium intervention, hypertension status, or trial duration. Sodium intervention included sodium intake reduction followed by administration of a sodium-containing supplement to one group (n=43), or diet modification aimed at sodium reduction (n=38). Follow-up ranged from 4 weeks to 36 months.

Main results

  • Sodium excretion was almost linearly associated with changes in SBP and DBP over the overall range of sodium intake, although the curve for SBP was steeper compared to the curve for DBP.
  • Overall, every 100 mmol/day reduction in urinary sodium excretion was associated with a mean reduction of 5.56 mmHg for SBP (95% CI: -4.52 to -6.95 mmHg) and 2.33 mmHg DBP (95% CI: -1.66 to -3.00 mmHg).
  • In trials that used supplementation of sodium, a 100 mmol/day reduction in sodium decreased the mean SBP by 4.47 mmHg (95% CI: -3.08 to -5.86 mm Hg) and DBP by 1.90 mm Hg (95% CI: -0.99 to -2.81 mmHg).
  • Every 100 mmol/day reduction in urinary sodium excretion by diet modifications decreased the mean SBP by 6.63 mmHg (95% CI: -5.12 to -8.15 mmHg) and DBP by 2.79 mmHg (95% CI: -1.80 to -3.78 mmHg).
  • Linear regression analysis in participants with hypertension showed that a 100 mmol/day decrease in sodium intake was associated with a 6.50 mmHg reduction in SBP (95% CI: -5.22 to -7.79) and 3.00 mmHg reduction for DBP (95% CI: -2.27 to -3.74). Individuals without hypertension showed a reduction of 2.30 mmHg SBP (95% CI: -1.33 to-3.27 mmHg) and 0.80 mmHg DBP (95% CI: +0.29 to -1.89).
  • When stratified for trial duration (4-11 weeks vs. ≥12 weeks), the effects on SBP were stronger in the short-term studies compared to the long-term trials. The dose-response slope for DBP was steeper at medium to high levels of sodium intake (>3 g/day) in the shorter studies compared to trials with a longer duration. The opposite effect was observed at lower levels of sodium intake (<3 g/day).
  • A larger difference in sodium intake was associated with a larger effect on SBP and DBP, most prominent for SBP and for both this was an almost linear association. Dietary changes had the strongest effect on SBP and DBP compared to sodium supplementation.
  • There was a stronger reduction in SBP and DBP with reduced sodium consumption in individuals with hypertension compared to those without hypertension. The relationship between sodium difference between the treatment arms and BP changes is linear in both groups.


This dose-response meta-analysis demonstrated a nearly linear relationship between sodium intake and mean SBP as well as DBP, without an indication of flattening of the curve at both ends of the sodium exposure range and independent of hypertension status and sodium exposure time. Dietary modifications had a stronger dose-response effect on SBP and DBP than sodium supplementation, with a steeper curve for SBP compared to DBP. The effect of sodium reduction on SBP was more prominent in individuals with hypertension than in those without.


1. Newberry SJ, Chung M, Anderson CAM, Chen C, Fu Z, Tang A, Zhao N, Booth M, Marks J, Hollands S, et al. Sodium and potassium intake: effects on chronic disease outcomes and risks: AHRQ comparative effectiveness reviews. Rockville, MD: Agency for Healthcare Research and Quality; 2018. doi: 10.23970/AHRQEPCCER206L

2. Graudal N, Hubeck-Graudal T, Jürgens G, Taylor RS. Dose-response relation between dietary sodium and blood pressure: a meta-regression analysis of 133 randomized controlled trials. Am J Clin Nutr. 2019;109:1273– 1278. doi: 10.1093/ajcn/nqy384

3. Kelly J, Khalesi S, Dickinson K, et al. The effect of dietary sodium modification on blood pressure in adults with systolic blood pressure less than 140 mmHg: a systematic review. JBI Database System Rev Implement Rep. 2016;14:196–237. doi: 10.11124/JBISRIR-2016-002410

4. Crippa A, Discacciati A, Bottai M, Spiegelman D, Orsini N. One-stage dose–response meta-analysis for aggregated data. Stat Methods Med Res. 2019;28:1579–1596. doi: 10.1177/0962280218773122 23.

5. Vinceti M, Filippini T, Malavolti M, Naska A, Kasdagli MI, Torres D, Lopes C, Carvalho C, Moreira P, Orsini N. Dose‐response relationships in health risk assessment of nutritional and toxicological factors in foods: development and application of novel biostatistical methods. EFSA support publ. 2020;17:EN‐1899. doi: 10.2903/sp.efsa.2020.EN‐1899

6. EFSA Panel on Nutrition, Novel Foods, and Food Allergens, Turck D, Castenmiller J, de Henauw S, et al. Dietary reference values for sodium. EFSA Journal. 2019;17:e05778. doi: 10.2903/j. efsa.2019.5778

Find this article online at Circulation

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