BACKGROUND: Chronic inflammation is a key driver of cardiovascular disease, the leading cause of death globally. Prior studies reported that high dietary salt increases pro-inflammatory cytokines such as circulating monocyte chemoattractant protein-1 (MCP-1), lipopolysaccharide (LPS) stimulated MCP-1, and interleukin-6 (IL-6) compared with low dietary salt in adults. Recent findings suggest concomitant nutritional ketosis (i.e., increased beta-hydroxybutyrate (β-OHB)) may promote an anti-inflammatory response in animals fed a high salt diet. Whether these protective effects of β-OHB translate to humans remains to be studied. Therefore, we examined inflammatory cytokine responses after short-term high salt and β-OHB supplementation in healthy adults. METHODS: Fourteen adults (11 M/3 F, age 27±4 years, BMI: 26±4 kg/m 2 ; mean±SD) completed a randomized, crossover study consisting of three 10-day conditions: low salt (LS): placebo capsules (dextrose) and placebo drink; high salt (HS): salt capsules and placebo drink; high salt + ketone (HS+K): salt capsules and ketone drink. Participants were counseled to consume a low sodium diet (~0.8 mg/kcal/day) for all conditions and supplemented with sodium (~2 mg/kcal/day) for HS conditions. Ketone monoester drinks provided 36 g β-OHB/day. We assessed circulating inflammatory cytokines C-reactive protein (CRP), IL-6, MCP-1, and tumor necrosis factor-α (TNF-α) in unstimulated plasma. We assessed IL-6, MCP-1, and TNF-α in plasma isolated from LPS stimulated (10 ng/mL for 2 hours @ 37°C) whole blood using ELISA. Depending on data normality, repeated measures ANOVA and Friedman test with median(IQR) are reported with α was set a priori at ≤0.05. RESULTS: In unstimulated plasma, we observed no effect of condition on circulating CRP (p=0.27), IL-6 (p=0.40), and MCP-1 (p=0.49) concentrations. Interestingly, we observe an effect of condition on circulating TNF-α concentration (LS: 1.28(0.66) vs HS: 1.00(0.57) vs HS+K: 1.19(0.55) pg/mL, p=0.02) with post hoc tests indicating that TNF-α concentration was lowered in the HS condition compared with LS (p=0.03). In LPS-stimulated blood, we observed no effect of condition on IL-6 (p=0.35) or MCP-1 (p=0.52) concentrations. However, we observed an effect of condition on stimulated TNF-α concentration (LS: 461.70(249.90) vs HS: 583.40(285.10) vs HS+K: 298.3(96.50) pg/mL, p=0.04) with post hoc tests indicating that TNF-α concentration was suppressed in the HS+K condition compared with HS (p=0.04). CONCLUSION: These preliminary findings indicate that in contrast to our hypothesis, salt did not increase unstimulated circulating cytokine concentrations. However, concomitant ketone supplementation may blunt salt-induced increases in TNF-α under inflammatory stimulation in apparently healthy adults. 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.
Jeong et al. (Fri,) studied this question.