Abstract

Introduction: Dietary nitrate improves cerebral blood flow and enhances physical performance by improving exercise capacity. We designed a proof-of-concept study to show increases in plasma nitrate and nitrite levels in ischemic stroke patients treated with beetroot juice shots vs placebo juice (nitrate removed). We assessed gait speed after 30 days and safety/adverse events with both groups. Methods: In a randomized placebo-controlled double-blind design, patients with NIHSS of ≥ 2 but < 20, with fair or good sitting balance and score >0 on hip flexion on the short Fugl-Meyer, within 5 days of stroke onset were enrolled. Those treated with IV alteplase or endovascular therapy, gait speed > 0.8 cm/sec, or taking nitrate-containing medications were excluded. After consent, patients were randomized to beetroot vs placebo juice. On days 1 and 30, blood was drawn for nitrate and nitrite levels before and one hour after drinking 70 cc (3.8 mM nitrate) beetroot juice (James White Fruit Juices) or an identically-appearing placebo juice, plus vitamin C 500 mg daily for 30 days in each group. On day 30, gait speed (using the 4 m walk) was assessed. Results: Eighteen participants (6 women, 12 men, 12 white, 4 African American and 2 other race-ethnicities, median age 64.6 IQR (58.7, 70.0)) were consented, 17 completed treatment (1 terminated treatment because of nausea), 16 followed for 30 days and 13 for 90 days. Baseline characteristics were balanced with regard to admission NIHSS (median 5.0 in each group), age, sex, race, risk factors, baseline gait speed (median 0.17 m/sec in active and 0.13 m/sec in placebo), and baseline nitrate/nitrite levels. There was no difference in adverse events in the two groups. The mean treatment-specific changes in nitrate were 236 micromoles/L (95% CI 170, 302) in the active and 0 (95% CI -64, 64) in the placebo group (p<0.0001). For nitrite, active group increased by 313 nanomoles/L (37, 588) and 20 nanomoles for placebo (-211, 252); p=0.045. Gait speed increased by 0.26m/sec in the active and 0.30m/sec in placebo group. Conclusions: Beetroot juice was associated with an increase in nitrate and nitrite levels, but was not associated with a change in gait speed after 30 days. Further studies with a larger population of stroke patients may be warranted.

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