# BEET root juice to reverse functional impairment in PAD: The BEET PAD Trial

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2023 · $656,986

## Abstract

BEETroot juice to reverse functional impairment in PAD: The BEET PAD Trial
 Our work and that of others demonstrate that people with lower extremity peripheral artery disease (PAD)
have greater functional impairment, more rapid functional decline, and faster mobility loss than those without
PAD. In PAD, lower extremity ischemia during walking activity increases gastrocnemius (calf) muscle oxidative
stress, damages myofibers, and induces calf muscle mitochondrial dysfunction. Yet few medical therapies
improve functional impairment or prevent mobility loss in PAD.
 Inorganic nitrate, abundant in beetroot juice, is a major source of nitric oxide (NO). In preclinical studies,
NO increases angiogenesis and perfusion, protects against ischemic injury, enhances mitochondrial activity,
and activates satellite cells, which restore and repair skeletal muscle. In three small pilot clinical trials,
including two by our co-investigator Dr. Jason Allen, oral nitrate or beetroot juice meaningfully improved
walking ability in people with PAD, compared to placebo. We propose a definitive multi-centered double-blind
randomized trial of beetroot juice vs. placebo in 210 people with PAD. We hypothesize that by increasing
lower extremity perfusion, calf muscle mitochondrial activity, and myofiber health and regeneration, beetroot
juice will improve walking performance in PAD. Our primary aim will determine whether, compared to placebo,
beetroot juice significantly improves six-minute walk at 4-month follow-up. In secondary aims, we will
distinguish acute from chronic effects of beetroot juice on six-minute walk and measure the effects of beetroot
juice on calf muscle perfusion, brachial artery flow-mediated dilation, physical activity (ActiGraph), the Walking
Impairment Questionnaire, and the short physical performance battery (SPPB).
 Nitrate in beetroot juice is metabolized to nitrite and subsequently to NO, attaining peak nitrite levels 2.5
hours after ingestion. Inter-individual variability exists in the extent of metabolic conversion of nitrate to nitrite.
Therefore, in a secondary aim, among PAD participants randomized to beetroot juice, we will determine
whether those who attain a higher peak or a greater increase in plasma nitrite 2.5 hours after beetroot juice
consumption have greater increases in six-minute walk at 4-month follow-up, compared to those who attain a
lower peak or a smaller increase in plasma nitrite. We will also measure the durability of beetroot juice effects,
by repeating six-minute walk distance 7 and 14 days after the final dose of beetroot juice or placebo. We will
perform calf muscle biopsy at baseline and follow-up to study the effects of beetroot juice on muscle
mitochondrial biogenesis and activity, mitophagy, capillary characteristics, and myofiber health.
 If beetroot juice improves functional performance and prevents functional decline in PAD, this widely
available and well tolerated therapy will have a major impact on preventing...

## Key facts

- **NIH application ID:** 10649671
- **Project number:** 5R01AG073257-02
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Mary McGrae McDermott
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $656,986
- **Award type:** 5
- **Project period:** 2022-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10649671

## Citation

> US National Institutes of Health, RePORTER application 10649671, BEET root juice to reverse functional impairment in PAD: The BEET PAD Trial (5R01AG073257-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10649671. Licensed CC0.

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