Nitrite Supplementation for Improving Physiological Function in Older Adults

• • Age 60-79 years. Women will be confirmed as postmenopausal (either natural or surgical) based on cessation of menses for >1 year.

    • Ability to provide informed consent
    • Score >22 on the mini mental state exam (MMSE) to allow a broad range of normal and mildly-impaired cognitive abilities, but function adequate to understand and complete trials (214)
    • Baseline brachial flow-mediated dilation (FMD) \< 7%Δ (rationale: non-invasive screening to ensure exclusion of subjects with exceptionally high baseline endothelial function(215))
    • Blood pressure (BP) >100/60 mmHg for past 3 mo (rationale: blood pressure below 100/60 mmHg may elevate the normally small risk of hypotension with sodium nitrite treatment)
    • Ability to perform motor and cognitive tests (e.g., can rise from a chair, walk for 2 min, climb 10 stairs)
    • Willing to accept random assignment to condition (older adults)

Exclusion Criteria:

• • High dietary nitrate intake or current nitrite supplementation; hypersensitivity to nitrates or nitrites

    • Glucose-6-phosphate dehydrogenase deficiency or blood methemoglobin >2%
    • Current smoking
    • Having past or present alcohol dependence or abuse, as defined by the American Psychiatry Association, Diagnostic and Statistical Manual of Mental Disorders
    • Body mass index (BMI) >40 kg/m2 (FMD measurements can be inaccurate in severely obese patients)
    • Chronic clinical diseases (e.g., coronary artery/peripheral artery/cerebrovascular diseases, diabetes, chronic kidney disease requiring dialysis, neurological disorders or diseases that may affect motor/cognitive functions [multiple sclerosis, Parkinson's disease, polio, Alzheimer's disease, dementia or other brain diseases of aging]), except hypertension and hyperlipidemia.
    • Regular vigorous aerobic/endurance exercise (>3 vigorous bouts/week)
    • Not weight stable in the prior 3 months (>2 kg weight change) or unwilling to remain weight stable throughout study (rationale: recent weight change or weight loss can influence vascular function and small metabolite signature(216))
    • Current treatment or recent cessation (\< 3 mo) of hormone replacement therapy.
    • Moderate or severe peripheral artery disease (ankle-brachial index \<0.7)(183)
    • A graded exercise test will be performed by all subjects, if there is physician concern or an adverse event, the subject will not participate in a maximal oxygen consumption test (this will be determined in accordance with stated contraindications for exercise testing provided by the American Heart Association)(217)
    • Claustrophobia, metal implants, etc., affecting feasibility and/or safety of the fMRI scanning.