When people take a supplement called inorganic nitrate, women’s bodies turn more of it into nitrite than men’s do — so women end up with higher levels of nitrite in their blood.

In healthy adult human males and females, participants receive a single oral dose of inorganic nitrate (e.g., 6.4 mmol sodium nitrate) and a matched placebo in random order, with washout periods. Plasma nitrite levels are measured at baseline and at 15, 30, 60, and 120 minutes post-ingestion. Sex differences in the magnitude and time course of nitrite elevation are statistically compared.

Healthy adult males and females are randomly assigned to receive inorganic nitrate supplementation (e.g., 6.4 mmol/day for 7 days) or placebo. Plasma nitrite levels are measured at baseline and day 7. The difference in nitrite increase between sexes is analyzed using an interaction term (sex × treatment) in a linear model.

A cohort of healthy adult males and females is recruited and given identical inorganic nitrate supplementation (e.g., 6.4 mmol/day for 3 days). Plasma nitrite levels are measured before and after supplementation. Sex is treated as a pre-specified stratification variable, and the difference in nitrite response is analyzed with adjustment for confounders (e.g., BMI, diet, hormonal phase).

In premenopausal females, plasma nitrite response to inorganic nitrate is measured during high-estrogen (follicular) and low-estrogen (luteal) phases, compared to males. This tests whether sex differences are driven by hormonal variation.

Erythrocytes or oral mucosal cells from male and female donors are exposed to identical concentrations of nitrate in culture. Nitrite production is measured over time to determine if sex differences in nitrate-to-nitrite conversion persist in isolated cells without systemic influences.