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The evidence
The science behind nitric oxide
One molecule touches nearly every system in the body. Here is the research — grouped by what it affects. Tap any area to read the studies.
Awarded the 1998 Nobel Prize in Medicine · 19 areas · 63+ references
Nitric oxide is the body's master signalling molecule for blood flow and vascular health. As it declines with age, system after system feels it. Below, each benefit links to peer-reviewed research — open studies, meta-analyses and reviews you can read yourself.
Cardiovascular
01 Heart healthNitric oxide keeps your arteries relaxed and flexible. Higher nitrate intake is linked to lower cardiovascular risk.
Research
- Lundberg, Weitzberg & Gladwin (2008). The nitrate–nitrite–nitric oxide pathway in physiology and therapeutics. Nature Reviews Drug Discovery.
- Lundberg, Carlström & Weitzberg (2018). Metabolic effects of dietary nitrate in health and disease. Cell Metabolism.
- Blekkenhorst et al. (2017). Dietary nitrate and atherosclerotic vascular disease mortality in older women. Am J Clin Nutr.
- Nobel Prize in Physiology or Medicine 1998 — nitric oxide as a cardiovascular signalling molecule.
02 Lowering blood pressureDietary nitrate and NO precursors produce measurable, repeatable drops in blood pressure — in healthy and hypertensive adults alike.
Research
- Webb et al. (2008). Acute blood pressure lowering, vasoprotective and antiplatelet properties of dietary nitrate. Hypertension.
- Kapil et al. (2015). Dietary nitrate provides sustained blood pressure lowering in hypertensive patients. Hypertension.
- Siervo et al. (2013). Inorganic nitrate and beetroot juice reduce blood pressure: systematic review & meta-analysis. J Nutr.
- Dong et al. (2011). Oral L-arginine supplementation and blood pressure: meta-analysis. Am Heart J.
- Barkhidarian et al. (2021). L-arginine and blood pressure: dose-response meta-analysis. Adv Nutr.
03 Cholesterol & artery healthIn people with high cholesterol, dietary nitrate improves the function of the artery lining and calms the inflammation that builds plaque.
Research
- Velmurugan et al. (2016). Dietary nitrate improves vascular function in hypercholesterolaemia: RCT. Am J Clin Nutr.
- Ashor et al. (2015). Inorganic nitrate/beetroot and endothelial function: systematic review & meta-analysis. Eur J Nutr.
- Khambata et al. (2017). Anti-inflammatory actions of inorganic nitrate stabilise the atherosclerotic plaque. PNAS.
- Bondonno et al. (2012). Nitrate-rich spinach augments NO status and improves endothelial function. Free Radic Biol Med.
Brain & metabolic
04 Brain health & dementiaNitric oxide raises blood flow to the brain, and loss of NO is mechanistically tied to cognitive decline and Alzheimer's changes.
Research
- Presley et al. (2011). Acute effect of a high-nitrate diet on brain perfusion in older adults. Nitric Oxide.
- Wightman et al. (2015). Dietary nitrate modulates cerebral blood flow and cognitive performance. Physiol Behav.
- Austin & Katusic (2013). Endothelial nitric oxide deficiency promotes Alzheimer's disease pathology.
- Katusic & Austin (2023). Endothelial nitric oxide in preservation of cognitive health. Stroke.
05 Reducing inflammationRestoring NO through the nitrate pathway lowers vascular inflammatory markers and helps inflammation resolve.
Research
- Khambata et al. (2017). Anti-inflammatory actions of inorganic nitrate stabilise the atherosclerotic plaque. PNAS.
- Carlström et al. (2010). Dietary nitrate reverses features of metabolic syndrome in eNOS-deficient mice. PNAS.
- Lundberg, Carlström & Weitzberg (2018). Metabolic effects of dietary nitrate in health and disease. Cell Metabolism.
06 Energy & mitochondriaNO helps build new mitochondria and makes them more oxygen-efficient — so your cells produce more energy from less oxygen.
Research
- Larsen et al. (2011). Dietary inorganic nitrate improves mitochondrial efficiency in humans. Cell Metab.
- Nisoli et al. (2003). Mitochondrial biogenesis in mammals: the role of endogenous nitric oxide. Science.
- Nisoli et al. (2004). Mitochondrial biogenesis by NO yields functionally active mitochondria. PNAS.
- Bailey et al. (2009). Dietary nitrate reduces the O₂ cost of exercise. J Appl Physiol.
07 Type 2 diabetes & metabolismMixed evidenceNO metabolism is impaired in diabetes; dietary nitrate reliably raises NO markers, though effects on blood sugar in established diabetes are mixed.
Research
- Gilchrist et al. (2013). Dietary nitrate on BP, endothelial function and insulin sensitivity in type 2 diabetes. Free Radic Biol Med.
- Bahadoran et al. (2015). Beneficial effects of inorganic nitrate/nitrite in type 2 diabetes: review.
- Carlström et al. (2010). Dietary nitrate reverses features of metabolic syndrome (eNOS-deficient mice). PNAS.
Performance & vitality
08 Exercise performanceBeetroot-derived nitrate lowers the oxygen cost of exercise and can improve endurance and high-intensity tolerance.
Research
- Bailey et al. (2009). Dietary nitrate reduces the O₂ cost of low-intensity exercise and enhances high-intensity tolerance. J Appl Physiol.
- Jones (2014). Dietary nitrate and the physiological determinants of exercise performance: a critical review. Appl Physiol Nutr Metab.
- Jones (2013). Dietary nitrate supplementation and exercise performance. Sports Med.
09 Erectile dysfunctionErections depend on the NO/cGMP pathway. NO precursors L-citrulline and L-arginine help mild-to-moderate erectile dysfunction.
Research
- Cormio et al. (2011). Oral L-citrulline improves erection hardness in men with mild ED. Urology.
- Chen et al. (1999). High-dose L-arginine in organic ED: double-blind RCT. BJU Int.
- Barassi et al. (2022). Long-term high-dose L-arginine in vasculogenic ED: RCT. J Endocrinol Invest.
- Rhim et al. (2021). L-arginine and PDE5 inhibitors in ED: meta-analysis. Andrologia.
10 Hormonal & reproductive signallingComplex scienceNO is a key messenger in the brain's control of reproductive hormones. Its role in steroid production is nuanced — not a simple 'testosterone booster'.
Research
- Rettori et al. (1993). Nitric oxide regulates luteinising hormone-releasing hormone secretion.
- McCann et al. (1996). The role of nitric oxide in reproduction.
- Zhang et al. (2021). Roles of nitric oxide in the regulation of reproduction: a review. Front Endocrinol.
- Del Punta et al. (1996). Nitric oxide inhibits Leydig cell steroidogenesis. Endocrinology.
11 ImmunityImmune cells use nitric oxide as a frontline weapon against viruses, bacteria, fungi and parasites.
Research
- MacMicking, Xie & Nathan (1997). Nitric oxide and macrophage function. Annu Rev Immunol.
- Bogdan (2001). Nitric oxide and the immune response. Nat Immunol.
- Nathan & Hibbs (1991). Role of nitric oxide synthesis in macrophage antimicrobial activity.
- Uehara et al. (2015). Nitric oxide in immune responses against viruses. Inflamm Res.
Specialised areas
12 Herpes & antiviralEmerging · lab researchIn laboratory studies, nitric oxide can suppress herpes simplex virus replication as part of the body's antiviral response.
13 Bone healthMixed evidenceNO helps regulate bone remodelling — supporting bone-building cells and restraining bone loss — though human trial results are mixed.
Research
- Wimalawansa (2010). Nitric oxide and bone. Ann N Y Acad Sci.
- Wimalawansa (2007). Rationale for nitric oxide donor therapy in osteoporosis.
- Jin et al. (2021). Nitric oxide modulates bone anabolism via osteoblast metabolism. J Clin Invest.
- Liu, Meng & Wang (2022). Efficacy of nitrates for bone health: systematic review & meta-analysis. Front Endocrinol.
14 Raynaud's phenomenonTopical NO donors increase blood flow to the fingers and reduce the frequency and severity of Raynaud's attacks.
Research
- Chung et al. (2009). Nitroglycerin (MQX-503) improves the severity of Raynaud's phenomenon: RCT. Arthritis Rheum.
- Hummers et al. (2013). Topical nitroglycerine gel in Raynaud phenomenon: RCT. Ann Rheum Dis.
- Curtiss et al. (2018). Topical nitrates in Raynaud's: systematic review & meta-analysis. J Am Acad Dermatol.
- Qiu et al. (2018). Nitroglycerin ointment for Raynaud's: systematic review. Rheumatol Int.
15 MenopauseEmergingNO availability falls through menopause as oestrogen drops. The NO precursor L-citrulline shows early benefit for blood-vessel function and blood pressure.
Research
- Moreau et al. (2012). Endothelial function is impaired across the stages of the menopause transition. J Clin Endocrinol Metab.
- Nyberg et al. (2020). Decline in endothelial function across the menopause transition; oxidative stress. GeroScience.
- Wong et al. (2022). L-citrulline on endothelial function and blood pressure in postmenopausal women. Nutrients.