Effect of Dietary Sodium on Blood Pressure: A Crossover Trial

Abstract

Importance: Dietary sodium recommendations are debated partly due to variable blood pressure (BP) response to sodium intake. Furthermore, the BP effect of dietary sodium among individuals taking antihypertensive medications is understudied.

Objectives: To examine the distribution of within-individual BP response to dietary sodium, the difference in BP between individuals allocated to consume a high- or low-sodium diet first, and whether these varied according to baseline BP and antihypertensive medication use.

Design, setting, and participants: Prospectively allocated diet order with crossover in community-based participants enrolled between April 2021 and February 2023 in 2 US cities. A total of 213 individuals aged 50 to 75 years, including those with normotension (25%), controlled hypertension (20%), uncontrolled hypertension (31%), and untreated hypertension (25%), attended a baseline visit while consuming their usual diet, then completed 1-week high- and low-sodium diets.

Intervention: High-sodium (approximately 2200 mg sodium added daily to usual diet) and low-sodium (approximately 500 mg daily total) diets.

Main outcomes and measures: Average 24-hour ambulatory systolic and diastolic BP, mean arterial pressure, and pulse pressure.

Results: Among the 213 participants who completed both high- and low-sodium diet visits, the median age was 61 years, 65% were female and 64% were Black. While consuming usual, high-sodium, and low-sodium diets, participants' median systolic BP measures were 125, 126, and 119 mm Hg, respectively. The median within-individual change in mean arterial pressure between high- and low-sodium diets was 4 mm Hg (IQR, 0-8 mm Hg; P < .001), which did not significantly differ by hypertension status. Compared with the high-sodium diet, the low-sodium diet induced a decline in mean arterial pressure in 73.4% of individuals. The commonly used threshold of a 5 mm Hg or greater decline in mean arterial pressure between a high-sodium and a low-sodium diet classified 46% of individuals as "salt sensitive." At the end of the first dietary intervention week, the mean systolic BP difference between individuals allocated to a high-sodium vs a low-sodium diet was 8 mm Hg (95% CI, 4-11 mm Hg; P < .001), which was mostly similar across subgroups of age, sex, race, hypertension, baseline BP, diabetes, and body mass index. Adverse events were mild, reported by 9.9% and 8.0% of individuals while consuming the high- and low-sodium diets, respectively.

Conclusions and relevance: Dietary sodium reduction significantly lowered BP in the majority of middle-aged to elderly adults. The decline in BP from a high- to low-sodium diet was independent of hypertension status and antihypertensive medication use, was generally consistent across subgroups, and did not result in excess adverse events.

Trial registration: ClinicalTrials.gov Identifier: NCT04258332.

Figure 1.. 24-Hour Ambulatory BP According to Allocated Diet Order and Study Visit

BP indicates blood pressure; DBP, diastolic blood pressure; MAP, mean arterial pressure; PP, pulse pressure; and SBP, systolic blood pressure. Delta values in blue or orange reflect median within-individual differences between diets, while delta values in black are mean differences between the high-sodium (HS) and low-sodium (LS) diet groups. Orange squares are median group values for each time point in those allocated to an LS diet first. Blue circles are median group values for each time point in those allocated to an HS diet first. Vertical bars indicate interquartile range. Between the groups randomized to an HS diet vs an LS diet first, at the end of the first diet week, mean differences in BP were as follows: SBP, 8 mm Hg (95% CI, 4-11 mm Hg; P < .001), DBP, 3 mm Hg (95% CI, 1-5 mm Hg; P = .01), MAP, 5 mm Hg (95% CI, 2-7 mm Hg; P = .001), and PP, 5 mm Hg (95% CI, 2-7 mm Hg; P = .001). ^aStatistically significant change.

Figure 2.. Distributions of Within-Individual 24-Hour Ambulatory BP Response to Dietary Sodium Intake, Calculated From High-Sodium Diet Minus Low-Sodium Diet

BP indicates blood pressure; DBP, diastolic blood pressure; MAP, mean arterial pressure; PP, pulse pressure; and SBP, systolic blood pressure. Bars above 0 reflect a reduction in BP during low-sodium diet vs high-sodium diet; bars below 0 reflect an increase in BP during low-sodium diet vs high-sodium diet. Percentages above 0 reflect proportion of individuals who experienced a reduction in BP during low-sodium diet vs high-sodium diet; percentages below 0 reflect proportion of individuals who experienced an increase in BP during low-sodium diet vs high-sodium diet. P values based on Wilcoxon signed rank test.

Figure 3.. Variation in Salt Sensitivity of Blood Pressure for MAP Across Subgroups

DBP indicates diastolic blood pressure; MAP, mean arterial pressure; and SBP, systolic blood pressure. Plot of within-individual salt sensitivity of blood pressure, calculated as the difference in MAP between high- and low-sodium diets. For each of the subgroups shown, the within-individual difference in MAP was significant at P < .001 for all except for non-CARDIA participants (P = .003) based on Wilcoxon signed rank tests with post hoc Bonferroni-corrected threshold for significance of P < .002. For each of the subgroup comparisons, eg, male vs female, the Wilcoxon rank sum tests were nonsignificant (P ≥ .10) for all except by DBP (P = .04). ^aCalculated as weight in kilograms divided by height in meters squared.

Figure 4.. Within-Individual 24-Hour Ambulatory BP Response to Low-Sodium vs High-Sodium Diets Stratified According to Baseline Hypertension Status

BP indicates blood pressure; DBP, diastolic blood pressure; MAP, mean arterial pressure; PP, pulse pressure; and SBP, systolic blood pressure. Change in BP was calculated as BP during high-sodium diet minus BP during low-sodium diet. Box center bars indicate medians; box tops and bottoms, IQRs; whiskers, the most extreme values within 75th percentile + 1.5 times IQR and 25th percentile − 1.5 times IQR; and circles, outliers. The within-individual salt sensitivity of BP response to high- minus low-sodium diets was similar between individuals with normotension (n = 49), controlled hypertension (n = 39), untreated hypertension (n = 50), and uncontrolled hypertension (n = 61).