Even if healthy middle-aged and older adults take the same amount of beetroot juice every day, some people still get more nitrite in their blood than others—so something else, like their mouth bacteria or genes, must be why they respond differently.

In healthy middle-to-older adults, compare plasma nitrite levels after 4 weeks of 380 mg/day nitrate from beetroot juice versus placebo, with washout periods, measuring variability within individuals across repeated cycles to confirm persistence of interindividual differences.

Track plasma nitrite response over 12 weeks of daily 380 mg nitrate supplementation in 100 healthy middle-to-older adults, measuring baseline and weekly nitrite levels, and correlate variability with pre-existing oral microbiome composition and genetic polymorphisms.

Aggregate individual participant data from existing RCTs of beetroot juice nitrate supplementation in middle-to-older adults to determine whether interindividual variability in plasma nitrite response remains significant after standardizing for dose and duration.

Test whether altering the oral microbiome (via antimicrobial mouthwash) abolishes variability in plasma nitrite response to 380 mg/day nitrate, confirming microbiome as a key driver of individual differences.

Compare oral microbiome and genetic profiles of individuals with the highest vs. lowest plasma nitrite response to identical 380 mg/day nitrate supplementation to identify distinguishing biological factors.