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October 18, 2025

Abstract TAC225: Ketone supplementation ameliorates high dietary salt-induced tumor necrosis factor-α secretion but not phenotypic shifts in myeloid cells in apparently healthy adults

BLBraxton A. LinderIndiana University Bloomington NSNina L. StuteAuburn University SJSoolim JeongIndiana University

Key Points

Ketone supplementation significantly reduced TNF-α secretion in high salt conditions, demonstrating an intriguing link to inflammation.
No changes in monocyte or dendritic cell phenotypes were observed, with both MCP-1 and IL-6 levels unaffected by treatments.
Fifteen healthy adults participated in a randomized, crossover study involving low salt, high salt, and high salt plus ketone conditions.
Findings suggest that while TNF-α levels can be moderated by ketones, myeloid cell profile changes were not influenced by high salt intake.

Abstract

Background: High salt ( HS ) consumption is a leading risk factor for cardiovascular disease, partly due to increased inflammation. Our group and others have demonstrated HS increases circulating Monocyte Chemoattractant Protein-1 ( MCP-1 ) and induces proinflammatory monocyte phenotypes. Preclinical data suggest that HS suppresses endogenous β-hydroxybutyrate ( b-OHB ) production, and restoring b-OHB blunts some negative consequences of HS, but effects on the immune system remain unclear. Therefore, we investigated whether concomitant b-OHB supplementation, with HS, could attenuate phenotypic drift in circulating myeloid cells in apparently healthy adults. Methods: 15 participants (10M/5F; Age:33±12yrs; BMI:24.9±3.2kg/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; High Salt ( 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. Separately, whole blood was stimulated with 10ng/mL lipopolysaccharide for 2 hours at 37C and plasma was assayed for MCP-1, interleukin-6 ( IL-6 ), and tumor necrosis factor-α ( TNF-α ). One-way repeated measures ANOVA (condition) were run for normally distributed data and Friedman’s test for non-normally distributed data. Significance was set to α≤0.05. Results: We observed no shifts in monocytes ( ps >0.079) or dendritic cells ( ps >0.124) across conditions. We did not observe differences in stimulated whole blood MCP-1 ( p =0.707) or IL-6 ( p =0.504) secretion across conditions. However, there was a condition effect on TNF-α secretion (LS:45856, HS:52857, HS+K:320±89, p =0.045) whereby ketone supplementation blunted the effect of HS ( p =0.039). Conclusions: Our preliminary findings suggest no effect of high salt or concomitant ketone supplementation on phenotypic changes in myeloid cells of apparently healthy adults. However, an effect on TNF-α secretion was observed post-inflammatory stimulus, suggesting that innate immune responses in healthy adults may reflect increased proinflammatory activity rather than subpopulation shifts.

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