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Randomized Controlled Trial
. 2025 Mar;13(6):e70284.
doi: 10.14814/phy2.70284.

The impact of dietary sodium and fructose on renal sodium handling and blood pressure in healthy adults

Affiliations
Randomized Controlled Trial

The impact of dietary sodium and fructose on renal sodium handling and blood pressure in healthy adults

Ronald K McMillan et al. Physiol Rep. 2025 Mar.

Abstract

Increased dietary sodium is linked to hypertension, but most young adults display "sodium-resistant" blood pressure (BP), meaning BP is not elevated with sodium loading. In sodium-resistant rodents, fructose induces salt-sensitive BP via increased renal sodium reabsorption. Therefore, we tested the impact of fructose and sodium on renal sodium handling and BP in healthy adults, hypothesizing that their combination would impair sodium excretion and increase BP. Thirty-six participants enrolled in a randomized, double-blind, crossover trial involving three diets varying in fructose and sodium. On day 7, participants wore ambulatory BP monitors and collected 24-h urine. Although high sodium increased urinary sodium excretion, excretion was 15% lower with high fructose plus high salt versus high salt alone (235.1 ± 85.0 vs. 277.9 ± 121.2 mmol/24 h, p = 0.05). Compared to the recommended diet, high salt alone did not significantly change 24 h. MAP; however, high fructose plus high salt modestly raised 24 h MAP (81 ± 6 vs. 84 ± 7 mmHg, p = 0.03). High fructose and high salt increased serum interleukin-6 concentrations compared to the recommended diet (0.31 ± 0.2 vs. 0.24 ± 0.19 pg/mL, p = 0.04). These findings suggest that increased sodium and fructose alter renal sodium handling and BP in young adults.

Keywords: Blood Pressure; Fructose; Renal Function; Salt.

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Conflict of interest statement

No conflicts of interest, financial, or otherwise, are declared by the authors.

Figures

FIGURE 1
FIGURE 1
Schematic figure of crossover dietary intervention.
FIGURE 2
FIGURE 2
Renal perturbation measures following each dietary intervention of recommended fructose plus recommended salt (RF + RS), recommended fructose plus high salt (RF + HS), and high fructose plus high salt (HF + HS). (a) 24‐h urinary sodium excretion N = 35. RM one‐way ANOVA: p < 0.0001. (b). 24‐h free osmolar clearance results following each dietary intervention N = 28. RM one‐way ANOVA: p < 0.0001. (c). 24‐h free water clearance results following each dietary intervention. N = 28. RM one‐way ANOVA: p = 0.001. Data are presented as individual and mean values. Significant differences were followed with post hoc pairwise comparisons using Tukey's multiple comparison.
FIGURE 3
FIGURE 3
24‐h ambulatory BP results following each dietary intervention of recommended fructose plus recommended salt (RF + RS), recommended fructose plus high salt (RF + HS), and high fructose plus high salt (HF + HS). (a) Mean Arterial Pressure. N = 33. RM one‐way ANOVA: p = 0.03. (b) Systolic blood pressure. N = 33 RM one‐way ANOVA: p = 0.04 (c). Nocturnal blood pressure dip. N = 33. RM one‐way ANOVA p = 0.009. Data are presented as individual and mean values. Significant differences were followed with post hoc pairwise comparisons using Tukey's multiple comparison.
FIGURE 4
FIGURE 4
Sex comparison of 24‐h ambulatory BP results following each dietary intervention of recommended fructose plus recommended salt (RF + RS), recommended fructose plus high salt (RF + HS), and high fructose plus high salt (HF + HS). (a) Mean arterial pressure. Males, N = 15, Females, N = 18. Two‐way ANOVA: Sex p = <0.001, Diet p = 0.04, Sex × Diet p = 0.90. (b) Nocturnal blood pressure dip. Males, N = 15 RM one‐way ANOVA: p = 0.02. (c) Nocturnal blood pressure dip. Females, N = 18, RM one‐way ANOVA: p = 0.12. Data are presented as mean values and SD for panel (a). Data are presented as individual and mean values for panels (b) and (c). Significant differences were followed with post hoc pairwise comparisons using Tukey's multiple comparison.
FIGURE 5
FIGURE 5
Assessment of IL6 in serum and the BP correlations. (a) Interleukin 6 levels detected in serum following each dietary intervention of recommended fructose plus recommended salt (RF + RS), recommended fructose plus high salt (RF + HS), and high fructose plus high salt (HF + HS). N = 30, RM one‐way ANOVA: p = 0.04. Data are represented as individual and mean values. Significant differences were followed with post hoc pairwise comparisons using Tukey's multiple comparison. (b) Correlations between each dietary intervention of recommended fructose plus recommended salt (RF + RS), recommended fructose plus high salt (RF + HS), and high fructose plus high salt (HF + HS) and the respective BP measures were analyzed using linear regression and significance was computed with a one‐tailed Pearson test.

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