Most nitric oxide supplements come in capsules or powders. CircO2 by Advanced Bionutritionals comes in sublingual lozenges — a delivery distinction that is not merely a marketing preference but a scientifically meaningful choice grounded in the Nobel Prize-winning research on how the body actually produces nitric oxide.
The body has two primary mechanisms for producing nitric oxide. The first — and most discussed — is the enzymatic pathway: endothelial cells produce NO from L-Arginine using the enzyme eNOS. This pathway produces NO in blood vessel walls in response to blood flow, acetylcholine signaling, and other stimuli.
The second pathway — less commonly discussed but equally important — is the nitrate-nitrite-nitric oxide pathway: dietary and supplemental nitrates are converted to nitrite by bacteria in the mouth and on the tongue, and this nitrite is then absorbed and converted to NO throughout the body, particularly in low-oxygen environments like exercising muscle tissue.
The 1998 Nobel Prize research identified this second pathway as critical to understanding how the body regulates blood vessel tone — and the sublingual delivery of CircO2 is specifically designed to leverage it.
Research has established that the bacterial community on the tongue's surface — primarily facultative anaerobes that can survive in both oxygen-rich and oxygen-poor environments — plays an essential role in the dietary nitrate pathway. These bacteria express nitrate reductase enzymes that convert salivary nitrate to nitrite, initiating the cascade that ultimately produces NO in tissues.
This is why antiseptic mouthwash use eliminates the cardiovascular benefits of dietary nitrates: it kills the oral bacteria performing this conversion. A study published in Free Radical Biology and Medicine found that regular antiseptic mouthwash use significantly increased blood pressure by eliminating the oral bacteria that participate in NO production from dietary nitrates.
CircO2's sublingual lozenge format delivers nitrate precursors directly to the oral environment where these bacteria are most concentrated — rather than swallowing capsules that must survive the acid environment of the stomach and the competitive metabolism of the small intestine.
CircO2 also contains Vitamin B12 in sublingual form — a delivery choice with its own substantial evidence base. Vitamin B12 absorption from oral supplements requires intrinsic factor — a protein produced by stomach cells whose production declines with age, proton pump inhibitor use, and certain autoimmune conditions. Sublingual B12 bypasses this gastric absorption requirement entirely by being absorbed through the mucous membranes under the tongue directly into the bloodstream.
Multiple studies have confirmed that sublingual B12 is as effective as intramuscular B12 injection for restoring B12 levels — making it the superior form for older adults or anyone with reduced intrinsic factor production.
"Regular antiseptic mouthwash use significantly increased systolic blood pressure compared to controls — demonstrating that oral bacteria performing nitrate-to-nitrite conversion are essential to the dietary nitrate pathway for NO production and blood pressure regulation."
— Free Radical Biology and MedicineBeyond the nitrate pathway, CircO2 also contains L-Citrulline — supporting the eNOS enzymatic pathway simultaneously. This dual approach addresses NO production through both major mechanisms: the dietary nitrate-oral bacteria pathway (via the sublingual delivery and nitrate precursors) and the L-Arginine-eNOS pathway (via L-Citrulline conversion to L-Arginine in the kidneys).
For adults over 60 — whose eNOS activity is significantly reduced — the nitrate pathway becomes proportionally more important as the enzymatic pathway declines. CircO2's formulation is particularly well-designed for this demographic.
CircO2 includes Hawthorn berry (Crataegus monogyna) — one of the most studied cardiovascular botanicals with a research history spanning over a century. Research in Cochrane Database of Systematic Reviews analyzed 14 randomized trials and confirmed that hawthorn extract significantly improved exercise tolerance and reduced symptoms in patients with heart failure. Mechanistically, hawthorn's oligomeric procyanidins and flavonoids improve coronary blood flow, reduce peripheral vascular resistance, and have mild ACE-inhibiting activity supporting blood pressure management.
CircO2 is manufactured by Advanced Bionutritionals, LLC, based in Norcross, Georgia — a company with decades of experience producing evidence-based nutritional supplements. The company's scientific advisory board includes credentialed researchers, and their product development philosophy emphasizes clinical evidence over marketing trends. This context matters for consumers evaluating supplement quality: the manufacturer's scientific standards influence formulation choices and quality control practices.
CircO2's sublingual delivery format is not a gimmick — it is a pharmacologically rational choice that leverages the oral microbiome's role in the nitrate-to-NO pathway, combined with the superior absorption characteristics of sublingual nutrient delivery. For adults whose eNOS-dependent NO production has declined with age, the oral nitrate pathway becomes increasingly important — making sublingual nitrate delivery a particularly well-designed approach for the over-60 demographic.
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