Dietary Supplements

A pilot randomized controlled trial of the effects of dietary nitrate supplementation on dynamic cerebral autoregulation in older adults with metabolic syndrome.

TL;DR

This pilot trial demonstrates the feasibility of dietary nitrate supplementation in MetS, and while no effects were observed in primary outcomes, exploratory analyses suggest potential region-specific improvements in dynamic cerebral autoregulation.

Key Findings

Beetroot juice supplementation successfully elevated plasma nitrate concentrations compared to placebo in older adults with metabolic syndrome.

  • Participants received nitrate-rich beetroot juice (BRJ) providing 6.4 mmol NO3- per day or nitrate-depleted placebo for 4 weeks
  • BRJ increased plasma nitrate concentrations versus placebo (p < 0.001)
  • The study was double-blind and placebo-controlled
  • Twenty-two older adults with MetS aged 55-75 years were randomized

The dietary nitrate supplementation intervention was well tolerated with high adherence among older adults with metabolic syndrome.

  • No significant safety or tolerability concerns were reported
  • High adherence to the 4-week supplementation protocol was observed
  • The trial successfully demonstrated feasibility of dietary nitrate supplementation in the MetS population
  • The double-blind, placebo-controlled design was maintained throughout the study

No significant effects of nitrate supplementation were observed on primary frontal dynamic cerebral autoregulation outcomes or cognition.

  • Primary analyses examined frontal dCA holistically using transfer function analysis (TFA) of beat-to-beat blood pressure and fNIRS-derived cerebral oxygenation
  • dCA was indexed by TFA phase and gain
  • No significant group differences were found for frontal dCA measures
  • Cognitive outcomes also showed no significant effects of the intervention

Exploratory analyses indicated region-specific differences in dynamic cerebral autoregulation in select frontal areas following nitrate supplementation.

  • Region-specific improvements were characterized by changes in both TFA phase and gain
  • These findings were limited to select frontal areas rather than the frontal region as a whole
  • These analyses were exploratory in nature and not primary outcomes
  • Functional near-infrared spectroscopy (fNIRS) was used to derive cerebral oxygenation measures enabling regional analysis

The study was designed based on the rationale that metabolic syndrome is associated with reduced nitric oxide bioavailability and impaired cerebrovascular function.

  • Metabolic syndrome was hypothesized to increase cognitive decline risk through impaired cerebrovascular function
  • Dynamic cerebral autoregulation maintains cerebral blood flow and may involve NO-related vascular mechanisms
  • Whether dietary nitrate supplementation influences dCA in MetS was previously unclear
  • Dietary nitrate is a precursor to nitric oxide via the nitrate-nitrite-NO pathway

What This Means

This research tested whether drinking nitrate-rich beetroot juice for four weeks could improve the brain's ability to regulate its own blood flow in older adults (ages 55-75) who have metabolic syndrome — a cluster of conditions including high blood pressure, high blood sugar, and excess body fat. The brain has a self-regulating system that keeps blood flow stable even when blood pressure changes, and this system may be weakened in people with metabolic syndrome, potentially raising the risk of cognitive decline. Twenty-two participants were randomly assigned to drink either beetroot juice or a placebo juice with the nitrate removed, and neither the participants nor the researchers knew who received which drink during the study. The beetroot juice successfully raised nitrate levels in participants' blood, and the intervention was well tolerated with high adherence — meaning the study design was practical and workable. However, when looking at the primary measures of brain blood flow regulation across the frontal region of the brain as a whole, no significant improvements were detected, and thinking and memory tests also showed no significant changes. In some specific smaller areas within the frontal brain region, there were exploratory hints of improvement in how the brain regulated blood flow, but these were secondary analyses in a small pilot study. This research suggests that a four-week beetroot juice intervention is feasible to conduct in older adults with metabolic syndrome, and the exploratory findings about region-specific brain blood flow regulation provide a rationale for larger, more definitive studies. The lack of significant effects on the primary outcomes means no firm conclusions can be drawn about whether dietary nitrate improves brain vascular health in this population, but the study lays groundwork for future research with larger sample sizes that could better detect potential benefits.

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Citation

Gosalia J, Spicuzza J, Bowlus C, Brinkerhoff A, Baker S, Qiu J, et al.. (2026). A pilot randomized controlled trial of the effects of dietary nitrate supplementation on dynamic cerebral autoregulation in older adults with metabolic syndrome.. Physiological reports. https://doi.org/10.14814/phy2.71073