Nitrite Supplementation for Improving Physiological Function in Older Adults

Inclusion Criteria:

- • 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.