Background: High salt (HS) consumption is a leading risk factor for cardiovascular disease, partly due to increased inflammation by increasing circulating proinflammatory cytokine concentrations. Preclinical data suggest that HS suppresses endogenous β-hydroxybutyrate (b-OHB) production, and restoring b-OHB blunts some negative consequences of HS. Separately, nutritional ketosis may improve adaptive immunity through metabolic reprogramming. However, the effects of both HS and b-OHB on the adaptive immune system remain unclear. Therefore, we investigated whether b-OHB supplementation could attenuate phenotypic drift in circulating T cell populations in apparently healthy adults consuming a HS diet. Methods: 15 participants (10M/5F; Age: 33 ± 12yrs; BMI: 24.9 ± 3.2 kg/m 2 ; blood pressure: 107 ± 13/63 ± 7mmHg) completed a randomized, crossover study with three 10-day conditions: Low Salt (LS): placebo capsules (dextrose) and placebo drink; HS: salt capsules and placebo drink; and High Salt + Ketone (HS+K): salt capsules and ketone drink. Participants received counseling to consume low-sodium (~0.8 mg/kcal/day) background diets for all conditions and were supplemented up to ~2 mg/kcal/day of sodium for HS conditions and 36g β-OHB/day for the ketone condition. On day 10, mononuclear cells were isolated from whole blood and stained via a Cytek 25-Color Immunoprofiling Assay. Populations of interest included; naïve (CD45+CD3+CD4+CD8-CCR7+CD45RA+), terminal Effector (CD45+CD3+CD4+CD45+CD3+CD4-CD8+CCR7-CD45RA-), and central memory (CD45+CD3+CD4+ CD45+CD3+CD4-CD8+CCR7+CD45RA-) CD4+ (helper T-cells (Th-cells)); naïve (CD45+CD3+CD4-CD8+CCR7+CD45RA+), terminal effector (CD45+CD3+CD8+ CD45+CD3+CD4-CD8+CCR7-CD45RA-), and central memory (CD45+CD3+CD8+CD45+CD3+CD4-CD8+CCR7+CD45RA-) CD8+ (cytotoxic T-cells (Tc-cells)); Treg (CD45+CD3+CD4+CD25+CD127-) and Treg activation state (Treg gMFI PD-1). Repeated measures ANOVA (condition) were run for normally distributed data (mean ± SD), and Friedman’s test for non-normally distributed data (median (IQR)). Significance was set at α ≤ 0.05. Results: We observed no shifts in Treg (CD3+CD4+CD25+CD127-) counts (ps > 0.173) or activation state (p = 0.291), nor shifts in naïve CD4+ (ps > 0.395), central memory CD4+ (ps > 0.286), naïve CD8+ (ps > 0.433), or central memory CD8+ (ps > 0.299) T cell subpopulations across conditions. We observed a significant effect of condition on CD4+ (LS: 0.73 ± 1.10%, HS: 0.46 ± 0.55%, HS+K: 0.91±1.43%, p = 0.050, η2 = 0.20) and CD8+ (LS: 0.22 (0.18)%, HS: 0.16 (0.13)%, HS+K: 0.18 ± (0.11)%, p = 0.033, η2 = 0.47) terminal effector T cell subpopulations with respect to the total CD45+ cell population. However, we observed no significant pairwise comparisons within either the CD4+ terminal effector T cell (ps > 0.063) or the CD8+ terminal effector T cell populations (ps > 0.091). Conclusions: Our preliminary data in humans suggest that HS and concomitant ketone supplementation may influence phenotypic changes in both helper and cytotoxic terminal effector T cells. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Linder et al. (Fri,) studied this question.