Dietary Nitrate Supplementation Improves Exercise Capacity and Endothelial Function in Subjects with COPD

by | Feb 22, 2024 | 2024, Fitness and Exercise, Lung Health

Written by Taylor Woosley, Science Writer. Findings of the systematic review and meta-analysis of 11 RCT studies show that dietary nitrate supplementation significantly improved exercise capacity, endothelial function through improved flow-mediated dilation, and reduced breathlessness in COPD subjects compared to placebo. 

lung x-rayChronic obstructive pulmonary disease (COPD) encompasses a group of disorders, including small airway obstruction, emphysema, and chronic bronchitis, and is characterized by chronic inflammation of the airways and lung parenchyma with progressive and irreversible airflow limitation1. COPD is accompanied by extrapulmonary comorbidities such as heart failure, osteoporosis, muscle atrophy, and cognitive impairment2. Major risk factors for COPD include cigarette smoking, sedentary lifestyle, and aging3.

Nitric oxide (NO) is a pluripotent signaling radical involved in many diverse physiological processes including vasoregulation, nerve transmission, and host defense4. Nitrate supplementation, which converts into NO through entero-salivary pathway in vivo, has been researched for its ability to improve exercise tolerance in people with COPD5. Evidence has shown that nitrate supplementation reduces systolic blood pressure and improves exercise capacity and endothelial function in COPD subjects6.

Wang et al. conducted a systematic review and meta-analysis to analyze the potential effects of dietary nitrate supplementation in COPD subjects, with a focus on exercise capacity. Study inclusion consisted of studies with participants clinically diagnosed with stable COPD without recent acute exacerbation and other major comorbidities including pulmonary hypertension, asthma, and pulmonary fibrosis, with a randomized controlled trial design comparing the efficacy of dietary nitrate supplementation with a placebo. Furthermore, studies included at least one of the following outcomes: plasma nitrate and nitrite concentrations, incremental shuttle walk test (ISWT), endurance shuttle walk time (ESWT), 6-min walk test (6MWT), fractional exhaled nitric oxide (FeNO), flow-mediated dilatation (FMD) and Borg dyspnea score.

11 studies were included in the final systematic review with 287 subjects with stable COPD. 9 studies followed a randomized controlled crossover trial design and two followed a randomized controlled study design. All studies used beetroot juice as the experimental intervention, except for one study which used sodium nitrate. Significant findings are as follows:

  • Of the 7 studies reporting on exercise capacity, findings show a statistically significant difference of the nitrate group over the placebo group (p = 0.03). Subgroup analysis results show a significant increase of exercise capacity in the ISWT subgroup compared to placebo (p = 0.02).
  • Of the 2 studies reporting on FMD in 158 subjects, results show that dietary nitrate increased FMD compared to placebo (p < 0.00001).
  • Of the 5 studies of 145 participants reporting on Borg dyspnea scores, findings show that the dietary nitrate group reduced dyspnea compared to placebo (p = 0.03).

Results of the systematic review and meta-analysis for 11 studies show that dietary nitrate supplementation significantly improved exercise capacity, plasma nitrite concentrations, flow-mediated dilation, and breathlessness. Further research should continue to explore the role of nitric oxide and nitrate supplementation on COPD symptoms. Study limitations include the significance of heterogeneity across the studies for certain outcomes (exercise capacity and plasma nitrate concentration), the different treatment durations of studies which may impact results, and the use of a limited number of studies which does not allow for more thorough subgroup analyses.

Source: Wang, Jing, Fanchao Feng, Yang Zhao, Le Bai, Yong Xu, Yun Wei, Hailang He, and Xianmei Zhou. “Dietary nitrate supplementation to enhance exercise capacity in patients with COPD: Evidence from a meta-analysis of randomized controlled trials and a network pharmacological analysis.” Respiratory Medicine 222 (2024): 107498.

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Posted February 22, 2024.

Taylor Woosley studied biology at Purdue University before becoming a 2016 graduate of Columbia College Chicago with a major in Writing. She currently resides in Glen Ellyn, IL.

References:

  1. Scoditti E, Massaro M, Garbarino S, Toraldo DM. Role of Diet in Chronic Obstructive Pulmonary Disease Prevention and Treatment. Nutrients. Jun 16 2019;11(6)doi:10.3390/nu11061357
  2. Wang T, Mao L, Wang J, Li P, Liu X, Wu W. Influencing Factors and Exercise Intervention of Cognitive Impairment in Elderly Patients with Chronic Obstructive Pulmonary Disease. Clin Interv Aging. 2020;15:557-566. doi:10.2147/cia.S245147
  3. Easter M, Bollenbecker S, Barnes JW, Krick S. Targeting Aging Pathways in Chronic Obstructive Pulmonary Disease. Int J Mol Sci. Sep 21 2020;21(18)doi:10.3390/ijms21186924
  4. Wisor JP, Holmedahl NH, Saxvig IW, et al. Effect of Dietary Nitrate Supplementation on Sleep in Chronic Obstructive Pulmonary Disease Patients. Nature and science of sleep. 2021;13:435-446. doi:10.2147/nss.S279395
  5. Yang H, He S, Chen F, Liang L, Pan J. Efficacy and safety of nitrate supplementation on exercise tolerance in chronic obstructive pulmonary disease: A systematic review and meta-analysis. Medicine (Baltimore). Jan 14 2022;101(2):e28578. doi:10.1097/md.0000000000028578
  6. Alasmari AM, Alsulayyim AS, Alghamdi SM, et al. Oral nitrate supplementation improves cardiovascular risk markers in COPD: ON-BC, a randomised controlled trial. The European respiratory journal. Feb 2024;63(2)doi:10.1183/13993003.02353-2022