The effects of inorganic nitrate and inulin co-ingestion on circulating metabolites and blood pressure in young adults: A pilot double-blind randomised crossover trial

Dietary patterns enriched in fermentable fibre (such as inulin) and inorganic nitrate are linked 26 to cardiovascular benefits, possibly mediated by gut microbiota-derived bioactive compounds 27 including short-chain fatty acids (SCFAs) and nitric oxide (NO). However, the potential synergistic 28 effects remain unclear. To address this knowledge gap, we conducted a randomised, double-blind, crossover study to investigate the acute effects of inulin (15 g; INU), nitrate (400 mg; NO3 - 29 ), and their combination (INU+NO3 - 30 ), on plasma nitrate and nitrite levels, SCFAs, and blood pressure (BP) in 20 normotensive participants. Plasma nitrate and nitrite were significantly elevated following INU+NO3 - 31 and NO3 - compared to INU (p < 0.001). Plasma SCFAs were increased after INU+NO3 - 32 and INU, 33 though the incremental area under the curve did not reach statistical significance, likely due to large 34 inter-individual variability. No significant main effects were observed on BP; however, inverse 35 correlations were identified between peak plasma nitrite and diastolic BP (rs = -0.61, p = 0.004) and mean arterial pressure (rs = -0.59, p = 0.005) following INU+NO3 - 36 . Peak nitrate concentrations were inversely correlated with diastolic BP following NO3 - 37 (rs = -0.47, p = 0.004). Although co38 supplementation with inulin and nitrate did not enhance plasma nitrate/nitrite or BP beyond nitrate 39 alone, it modulated SCFAs profiles, suggesting potential interactions between fibre fermentation and 40 nitrate metabolism for cardiovascular health.