Can nutrition strategies, such as fiber and ketone supplementation, ameliorate the negative effects of high salt consumption on vascular health and immune cell phenotypes?

Abstract

Background: Consuming high dietary salt (HS) is prevalent in the western diet and does not appear to be decreasing. HS consumption is the leading modifiable risk factor for the development of hypertension and subsequent cardiovascular disease (CVD) in the United States. Understanding that CVD is the leading cause of death, strategies are necessary to reduce the risk of CVD development. Dietary fiber and the ketone body β-hydroxybutyrate (βHB) have been demonstrated to be candidate nutrients in supporting cardiovascular health and reducing inflammation. Therefore, the purpose of this dissertation was to investigate the potential roles of dietary fiber and βHB in offsetting the negative effects of high dietary salt consumption and exposure. Methods: To investigate the role of fiber, a national dataset (NHANES) was collected from the Center of Disease Control; dietary patterns were quantified by total sodium consumption and sodium indexed to fiber and were correlated with blood pressure (BP) and markers of inflammation. A clinical trial was used to investigate the effect of βHB supplementation on BP reactivity, a measure prognostic of future CV incidence regardless of salt sensitivity status, despite concomitant salt supplementation; and a cell culture model was used to investigate whether direct βHB exposure would ameliorate the proinflammatory response induced by high salt observed in peripheral blood mononuclear cells. Results: While no linear relations were observed between recalled nutrition and measured BP, there were quadratic relations between sodium to fiber and all measures of BP (ps < 0.035). The clinical 2 trial remains underpowered at the time of this writing, and no significant effects of supplemental conditions were observed on BP reactivity, however the proinflammatory cytokine TNF-α was reduced in the HS+βHB condition (p = 0.035). There was a significant effect of the βHB exposure in the expression of pro- (p < 0.001) and anti-inflammatory (p = 0.008) cytokines the immune cells. Conclusion: Observing sodium to fiber ratios may provide an index into dietary habits, but are not linearly related to BP. With continued investigation βHB may provide cardioprotective benefits and has been demonstrated to decrease proinflammatory gene expression.