Dietary Supplements

Acute dietary nitrate supplementation attenuates caffeine-induced increase in arterial stiffness in healthy adults: a randomized cross-over trial.

TL;DR

Acute NO3- supplementation offset caffeine-induced increases in arterial stiffness variables, improving understanding of the cardiovascular health benefits afforded by acute NO3- consumption under cardiovascular strain.

Key Findings

Caffeine supplementation increased augmentation pressure and augmentation index compared to placebo and beetroot, but nitrate-rich beetroot plus caffeine did not differ from placebo.

  • Augmentation pressure was higher following CAF (+3(2) mmHg) than PL (+1(3) mmHg) and BR (+0(3) mmHg; P < 0.001–0.007)
  • Augmentation index was higher following CAF (+10(9)%) than PL (+4(11)%) and BR (+1(11)%; P < 0.001–0.007)
  • BR-CAF augmentation pressure (+1(3) mmHg) and augmentation index (+3(10)%) did not differ from PL or BR (P = 0.505–0.689)
  • This indicates nitrate-rich beetroot attenuated the caffeine-induced increase in arterial stiffness markers

Nitrate-rich beetroot supplementation elevated plasma nitrite concentrations compared to placebo and caffeine-only conditions.

  • Plasma nitrite was higher in BR and BR-CAF than PL and CAF (P < 0.001)
  • Nitrate-rich beetroot powder contained 400 mg NO3- versus NO3--depleted powder containing 92 mg NO3-
  • Elevated plasma nitrite suggests successful conversion of dietary nitrate to nitrite via the enterosalivary pathway
  • No between-group differences were observed in plasma cyclic guanosine monophosphate (cGMP; P = 0.370)

Brachial blood pressure, central blood pressure, and macrovascular endothelial function were not significantly altered by beetroot or caffeine supplementation compared to placebo.

  • Brachial BP, central BP, and macrovascular endothelial function were not altered with BR or CAF compared to PL (P = 0.067–0.359)
  • Macrovascular endothelial function was assessed post-supplementation using flow-mediated dilation (FMD)
  • Blood pressure and FMD measurements were taken pre- and post-supplementation at 2.5 hours
  • The absence of BP changes suggests caffeine's cardiovascular strain was primarily reflected in arterial stiffness rather than blood pressure at this timepoint

The study used a randomized, double-blind, placebo-controlled crossover design with four experimental trials in healthy adults.

  • Twenty-four healthy participants completed all four trials (17 males; age: 24(3) years)
  • The four conditions were: nitrate-rich beetroot + caffeine (BR-CAF), nitrate-rich beetroot alone (BR), caffeine alone (CAF), and placebo (PL)
  • Caffeine dose was 6 mg kg-1 body mass
  • Nitrate-rich beetroot powder provided 400 mg NO3- and nitrate-depleted powder provided 92 mg NO3-
  • Measurements were taken pre- and 2.5 hours post-supplementation

The lack of change in plasma cGMP despite elevated plasma nitrite in the beetroot conditions suggests the nitrate-mediated attenuation of arterial stiffness may not be fully explained by the canonical nitrate-nitrite-NO-cGMP signaling pathway.

  • There were no between-group differences in plasma cGMP (P = 0.370)
  • Plasma nitrite was significantly elevated in BR and BR-CAF versus PL and CAF (P < 0.001)
  • cGMP is a downstream messenger of nitric oxide (NO) signaling and would be expected to rise if NO bioavailability increased
  • The dissociation between plasma nitrite and cGMP levels raises questions about the mechanistic pathway underlying the observed vascular effects

What This Means

This research suggests that drinking nitrate-rich beetroot powder before consuming caffeine can prevent the increase in arterial stiffness that caffeine typically causes. Arterial stiffness — measured here by augmentation pressure and augmentation index — reflects how hard the heart has to work to pump blood and is associated with cardiovascular health risk. In this study, caffeine alone made arteries noticeably stiffer, but when participants consumed nitrate-rich beetroot powder along with caffeine, their arterial stiffness remained similar to when they took a placebo with no caffeine at all. Interestingly, the nitrate-rich beetroot did not change blood pressure or a measure of how well blood vessels dilate (flow-mediated dilation) in any condition. The beetroot supplement did successfully raise blood levels of nitrite, a molecule the body converts from dietary nitrate and which can be further converted to nitric oxide — a compound known to relax blood vessels. However, levels of a key signaling molecule (cGMP) that would normally increase alongside nitric oxide activity did not change, leaving the exact biological mechanism unclear. This research matters because caffeine is one of the most widely consumed substances in the world, and some people may have concerns about its cardiovascular effects. The findings suggest that dietary nitrate — found naturally in foods like beetroot, spinach, and rocket — might help counteract some of caffeine's acute effects on vascular stiffness. However, because this was a short-term study in young, healthy adults, further research would be needed to understand whether these effects apply to older individuals or those with existing cardiovascular conditions.

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Citation

McLellan A, Ahmad N, Acton J, Punni H, O'Donnell E, Shepherd A, et al.. (2026). Acute dietary nitrate supplementation attenuates caffeine-induced increase in arterial stiffness in healthy adults: a randomized cross-over trial.. Food &amp; function. https://doi.org/10.1039/d6fo02338j