Nitric oxide (NO) is a gaseous signaling molecule that your endothelial cells produce to relax blood vessels, improve blood flow, and regulate blood pressure. It’s essential for cardiovascular health, exercise performance, sexual function, and even cognitive clarity. The problem: NO production declines significantly with age, poor diet, and sedentary lifestyle.
If you are over 50 and considering NO support, our guide to nitric oxide boosters for older adults covers what to look for.
The 1998 Nobel Prize in Medicine was awarded for the discovery of nitric oxide’s role in cardiovascular signaling — this isn’t fringe science. NO-boosting supplements are among the most well-supported performance and health interventions available.
How Nitric Oxide Production Works
Your body produces NO through two primary pathways:
The L-Arginine-NOS Pathway
The enzyme nitric oxide synthase (eNOS) converts L-arginine into nitric oxide and L-citrulline. This is the primary pathway in healthy, younger individuals. However, eNOS activity declines with age, oxidative stress, and endothelial dysfunction.
The Nitrate-Nitrite-NO Pathway
Dietary nitrates (from beetroot, leafy greens) are converted by oral bacteria to nitrite, then reduced to NO in acidic environments (stomach) and hypoxic tissues. This pathway becomes increasingly important as the eNOS pathway declines with age. Critical note: antiseptic mouthwash kills the oral bacteria needed for this pathway — a significant and underappreciated issue.
Top NO-Boosting Compounds
L-Citrulline
Paradoxically more effective than L-arginine at raising blood arginine and NO levels because it bypasses first-pass liver metabolism. Clinical dose: 3–6 g/day (or 6–8 g as citrulline malate). A 2019 systematic review confirmed significant improvements in exercise performance and blood pressure. Best for: exercise performance and sustained NO production.
Beetroot Extract / Beetroot Juice
Rich in dietary nitrates that feed the nitrate-nitrite-NO pathway. A 2017 meta-analysis in Nutrients found beetroot supplementation improved endurance exercise performance by 3–5% and reduced blood pressure by 3–10 mmHg. Clinical dose: 400–800 mg nitrate (equivalent to ~500 mL beetroot juice or concentrated shots). Best for: endurance athletes and blood pressure support.
L-Arginine
The direct substrate for eNOS. Less effective orally than citrulline due to extensive first-pass metabolism, but still useful at 3–6 g/day, especially in combination with citrulline. Best for: combined stacks where it complements citrulline.
S7® Plant-Based NO Booster
A patented blend of seven plant extracts (green coffee bean, green tea, turmeric, tart cherry, blueberry, broccoli, kale) clinically shown to increase NO levels by 230% at just 50 mg/day. Works by upregulating eNOS expression. Best for: a low-dose, stimulant-free NO boost in capsule form.
Best Nitric Oxide Supplements by Category
Best Overall: HumanN SuperBeets Heart Chews
Clinically studied beetroot-based chews delivering concentrated dietary nitrates. Convenient, great-tasting, and backed by the company founded by NO research pioneer Dr. Nathan Bryan. Also contains grape seed extract for additional vascular support. Best for: daily cardiovascular NO support without powders or pills.
Best for Exercise Performance: Transparent Labs Bulk Pre-Workout
Contains 8 g citrulline malate, 200 mg S7®, and performance-dosed beta-alanine, betaine, and taurine. Fully transparent label — every ingredient and dose visible. Third-party tested. Best for: gym performance with maximum NO and pump support.
Best Pure L-Citrulline: Nutricost L-Citrulline 3g
Simple, unflavored L-citrulline powder. 3 g per scoop, 120 servings per container. Third-party tested, no fillers or additives. Mix into any beverage. Best for: customizable dosing for experienced supplement users.
Best Beetroot Powder: HumanN BeetElite
Concentrated beetroot crystals delivering 6 g of fermented beetroot per serving (equivalent to 6 whole beets). Designed for athletes — used by over 120 professional and college sports teams. Best for: endurance athletes who want concentrated nitrate loading.
Best Capsule Formula: Zhou N.O. Pro
Combines beetroot extract, L-citrulline, L-arginine, and grape seed extract in a convenient capsule format. No mixing required. Best for: people who want NO support without powders or drinks.
Nitric Oxide and Aging: Why It Matters After 40
NO production declines roughly 10–12% per decade after age 25. By age 50-60, many people have lost 50%+ of their NO-producing capacity. This decline contributes to:
- Elevated blood pressure — blood vessels lose their ability to relax
- Reduced exercise capacity — impaired oxygen delivery to working muscles
- Cognitive decline — decreased cerebral blood flow
- Erectile dysfunction — one of the earliest signs of endothelial dysfunction
- Increased cardiovascular risk — endothelial dysfunction is a root cause of atherosclerosis
Supplementing with both citrulline (for the eNOS pathway) and beetroot (for the nitrate pathway) provides dual-pathway support — especially important as you age.
Frequently Asked Questions
What’s better for nitric oxide: citrulline or arginine?
L-citrulline is superior for raising blood arginine and NO levels because it bypasses first-pass liver metabolism. Arginine taken orally is significantly degraded by arginase enzymes in the gut and liver before reaching systemic circulation. Citrulline is converted to arginine in the kidneys, delivering it directly to the bloodstream.
Can nitric oxide supplements lower blood pressure?
Yes. Both beetroot-derived nitrates and citrulline have shown clinically significant blood pressure reductions in multiple meta-analyses — typically 3–10 mmHg systolic. However, if you’re on blood pressure medication, consult your doctor as the effects can be additive.
Do NO supplements help with erectile dysfunction?
Nitric oxide is the primary mediator of erections — it’s the same pathway that Viagra (sildenafil) targets. While NO supplements are not as potent as PDE5 inhibitors, citrulline (1.5–3 g/day) has shown mild improvements in erectile hardness in clinical studies, particularly for mild ED.
Should I stop using mouthwash if I take beetroot supplements?
Antibacterial mouthwash kills the oral bacteria (Veillonella, Actinomyces) essential for converting dietary nitrate to nitrite. Studies show mouthwash use can reduce the blood pressure-lowering effects of beetroot by up to 100%. Consider switching to non-antibacterial mouthwash or simply rinsing with water.
When should I take nitric oxide supplements?
For exercise: 30–60 minutes before training. For blood pressure and general health: split doses morning and evening for sustained levels. Beetroot is most effective when taken 2–3 hours before peak demand due to the nitrate conversion timeline.
The Bottom Line
Nitric oxide supplementation addresses a genuine age-related decline with strong clinical evidence for cardiovascular, performance, and cognitive benefits. A dual-pathway approach — citrulline for the eNOS pathway and beetroot for the nitrate pathway — provides the most comprehensive support, especially for adults over 40.
This article is for informational purposes only and does not constitute medical advice. Consult your healthcare provider before starting any new supplement regimen.
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- Oral toxicological studies of pueraria flower extract: acute toxicity study in mice and subchronic toxicity study in rats. Journal of food science. 2013. PMID: 24245900.
- Evaluation of the vascular remodeling markers elastin, vascular endothelial growth factor A (VEGF-A), vascular endothelial growth factor receptor 2 (VEGFR2), and nitric oxide in patients with varicose veins. Kardiochirurgia i torakochirurgia polska = Polish journal of cardio-thoracic surgery. 2025. PMID: 41684764.
- Glial and neuronal control of brain blood flow. Nature. 2010. PMID: 21068832.
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