Nitrate, exercise and vascular function in midlife women

Wider research context Advancing age is a major risk factor for cardiovascular disease (CVD). In women, the decline in the sex hormone oestrogen with menopause contributes to impaired vascular function and an increased CVD risk, in part via a reduced bioavailability of the endothelium-derived signaling molecule nitric oxide (NO), chronic low-grade inflammation and increased oxidative stress. Aerobic exercise training is a key lifestyle strategy to prevent CVD. However, data indicate that exercise is less effective for improving cardiovascular (CV) health in postmenopausal women as compared with men of similar age. Oestrogen treatment may restore vascular training adaptations but is associated with health risks. The main objective of this research is to examine whether dietary nitrate as a nutritional ‘adjuvant’ to regular exercise could be an innovative lifestyle intervention to favorably modulate vascular training adaptations and health in midlife women. This proposal expands upon findings by our group and others showing that inorganic nitrate from vegetables exerts benefits on physical function and CV health by increasing NO availability through the nitrate–nitrite–NO pathway and by attenuating inflammation and oxidative stress. Objectives and hypotheses We propose a clinical study to examine whether the daily consumption of nitrate-rich (HI-NI) beetroot juice (BRJ) concomitant with aerobic exercise training improves vascular function, blood pressure, and CV fitness in postmenopausal women more effectively as compared with nitrate-depleted (LO-NI) BRJ consumption. Our hypothesis is that the increased nitrate intake favorably modulates the systemic inflammatory and oxidative stress status and promotes CV health-related outcomes of training. Methods This study will involve a prospective, randomized, placebo-controlled parallel-group design. 54 sedentary postmenopausal women (45-65 years) will be recruited and randomized into two groups. Both groups will undergo 12 weeks of exercise training. One group will receive HI-NI BRJ, and the other LO-NI BRJ (as placebo). 42 participants (21 per group) will be required to complete the study, based on power/sample size calculations with the forearm blood flow response to acetylcholine as primary endpoint. Principal secondary endpoints will be 24 h-ambulatory blood pressure and maximal oxygen uptake. Additional measures will include blood inflammation and oxidative stress biomarkers. Originality and innovation We anticipate that this work will provide important new evidence on the efficacy of dietary nitrate to improve the training responsiveness, vascular function and health in women after menopause.