Dietary Ketones are an Emerging Strategy to Attenuate the Adverse Cardiorenal Effects of Short-Term High Salt Loading

Abstract

Background: Excessive dietary salt is a major risk factor for hypertension, metabolic syndrome, and impaired renal function. Recent studies suggest protective cardiorenal effects of exogenous ketone supplementation; however, these findings are mostly derived from animal models. Therefore, the purpose of this dissertation was to 1) cover the mechanisms between salt and cardiorenal health; and 2) examine whether high salt and ketone supplementation may offset the adverse effects of high salt in young adults. Methods: Fifteen participants (11 Males/4 Females, age 27 ± 4 years, body mass index: 26 ± 4 kg/m2) were analyzed from our randomized, crossover study. Participants completed three 10-day conditions: A) low salt: dextrose capsules and placebo drink; B) high salt: salt capsules and placebo drink; and C) high salt + ketone: salt capsules and ketone drink. We assessed changes in blood pressure (BP), renal blood velocity (RBV), and renal vascular resistance (RVR) at baseline and during sympathoexcitatory maneuver. Acute kidney injury (AKI) biomarkers neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) indexed to urine flow rate were assessed. The product of insulin-like growth factor binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinase-2 (TIMP-2) including the renin-angiotensin-aldosterone system were also assessed. Depending on data normality, repeated measures ANOVA or the Friedman test and mean ± SD or median(IQR) are reported with significance set at p ≤ 0.05. Results: BP did not differ between conditions (ps≥0.62). There were no differences in baseline RBV (p=0.65) or RVR (p=0.79). No effects of diet were observed during sympathoexcitatory maneuver for MAP (p=0.89), RBV (p=0.71), and RVR (p=0.26). Sodium excretion increased with salt loading (p=0.04). There were no changes across conditions for AKI biomarkers including NGAL (p=0.59), KIM-1 (p=0.50), and IGFBP7*TIMP-2 (p=0.81) or in creatinine clearance (p=0.59). Plasma renin activity remained unchanged across conditions (p=0.16). However, aldosterone was suppressed with salt loading (p=0.01), with no difference between the high salt and ketone conditions. Conclusion: In our preliminary data, we did not observe significant changes in cardiorenal outcomes following high salt and ketone supplementation in healthy, salt-resistant younger adults. Additional data, particularly in salt-sensitive individuals, is needed to confirm our findings.