nitric oxide

Nitric oxide (NO) is a gaseous signaling molecule produced in the vascular endothelium and mitochondria, which dilates blood vessels, improves blood flow, and plays a key role in tissue regeneration - -and red light directly and measurably increases its production.

Nitric oxide, with the chemical formula NO, is a simple diatomic molecule that in the human body does not function as a toxic gas, but as a biological signaling messenger with an exceptionally wide range of effects. It belongs to the so-called gasotransmitters - gaseous molecules that the body deliberately produces and uses to coordinate biological processes in cells, blood vessels, and the nervous system.

Nitric oxide was discovered as an endogenous biologically active molecule in 1987, and its researchers Robert Furchgott, Louis Ignarro, and Ferid Murad were awarded the Nobel Prize in Physiology or Medicine in 1998 for this discovery. Today, NO is one of the most intensively studied signaling molecules in biomedicine - and also one of the key mechanisms through which photobiomodulation acts on the human body.

Where and how the body produces nitric oxide

The body produces NO both enzymatically and non-enzymatically from several sources:

Enzymatic synthesis via NOS (NO synthase)
The primary pathway is the enzymatic conversion of the amino acid L-arginine into L-citrulline with the formation of NO. This process is catalyzed by enzymes called nitric oxide synthases (NOS). There are three main isoforms: endothelial (eNOS), neuronal (nNOS), and inducible (iNOS). Endothelial NOS is located directly in the inner lining of blood vessels (the endothelium) and ensures continuous basal production of NO, which is essential for the regulation of vascular tone.

Photodissociation from mitochondria during light therapy
Under normal conditions, part of NO binds to the enzyme cytochrome c oxidase (CCO) in the mitochondrial respiratory chain. This binding inhibits CCO and slows down the production of ATP. Red and near-infrared light (especially wavelengths of 620 to 680 nm and 810 to 850 nm) break this bond - NO is released from CCO and becomes biologically available. At the same time, the unblocking of CCO results in increased ATP production.

Release from blood reservoirs
NO is also released from nitrosylhemoglobin (HbNO) and S-nitrosothiols (RSNO) in blood reservoirs - red blood cells and plasma. Research from 2022 confirmed that red light at 670 nm releases NO from these reservoirs independently of NOS enzymes, representing a mechanism distinct from enzymatic synthesis. [R]

Biological effects of nitric oxide

NO is a molecule with an exceptionally wide range of biological effects. Below are the most important ones from the perspective of health and red light therapy:

Vasodilation and improved blood flow
The primary and most well-documented effect of NO is the relaxation of smooth muscle in the vessel wall, resulting in vasodilation — the widening of blood vessels. This vasodilation lowers blood pressure, improves microcirculation, and increases the supply of oxygen and nutrients to tissues. A clinical study documented that exposure to 670 nm red light (50 mW/cm², 5 to 10 minutes) induced measurable vasodilation, with blood flow remaining elevated for 30 minutes after the exposure ended. [R]

Unblocking cytochrome c oxidase and increasing ATP
When NO is released from CCO (where it acts as a compet

Where and how the body produces nitric oxide

The body produces NO both enzymatically and non-enzymatically from several sources:

Enzymatic synthesis via NOS (NO synthase)
The main pathway is the enzymatic conversion of the amino acid L-arginine into L-citrulline with the formation of NO. This process is catalyzed by enzymes called nitric oxide synthases (NOS). There are three main isoforms: endothelial (eNOS), neuronal (nNOS), and inducible (iNOS). Endothelial NOS is localized directly in the inner lining of blood vessels (the endothelium) and ensures continuous basal production of NO important for regulating vascular tone.

Photodissociation from mitochondria during light therapy
Under normal conditions, part of NO binds to the enzyme cytochrome c oxidase (CCO) in the mitochondrial respiratory chain. This binding inhibits CCO and slows down the production of ATP. Red and near-infrared light (especially wavelengths of 620 to 680 nm and 810 to 850 nm) breaks this bond - NO is released from CCO and becomes biologically available. At the same time, the unblocking of CCO results in increased ATP production.

Release from blood reservoirs
NO is also released from nitrosylhemoglobin (HbNO) and S-nitrosothiols (RSNO) in blood reservoirs - red blood cells and plasma. Research from 2022 confirmed that red light at 670 nm releases NO from these reservoirs independently of NOS enzymes, representing a mechanism distinct from enzymatic synthesis. [R]

itively as a competitive inhibitor of oxygen), the enzyme resumes normal function. Electron flow in the respiratory chain is restored, the mitochondrial membrane potential increases, and the production of ATP rises. This is one of the main mechanisms through which photobiomodulation increases cellular energy. [R]

Anti-inflammatory effects
NO inhibits lipid peroxidation - a process in which free radicals damage cell membranes. At the same time, it modulates the expression of inflammatory cytokines and reduces the adhesion of inflammatory cells to the vascular endothelium. Research has confirmed that combined red and NIR light therapy increases NO bioavailability while reducing the production of superoxide radicals and the expression of the inflammatory marker ICAM-1.

Cardioprotection and neuroprotection
NO plays a critical role in protecting cardiac and nervous tissue from ischemia and reperfusion injury. Studies document that red light at 670 nm, by releasing NO from blood reservoirs, protects myocardial tissue in ischemia-reperfusion models. Similar neuroprotective effects have been documented with transcranial application of NIR light. [R]

Stimulation of insulin secretion and metabolic regulation
NO releases calcium from mitochondria, thereby stimulating insulin secretion and activating ion channels. This pathway is one of the explanations for why red light therapy shows positive effects on glycemic regulation.

Wound healing and tissue regeneration
Increased NO bioavailability after photobiomodulation accelerates angiogenesis (formation of new blood vessels), migration of inflammatory cells into the wound, and collagen production. A clinical study on human skin confirmed that exposure to 670 nm and 850 nm light (45 J/cm², 50 mW/cm², 15 minutes) statistically significantly increased NO release from intact human skin at all tested wavelengths.

NO and photobiomodulation: a dual mechanism

The relationship between nitric oxide and photobiomodulation has two aspects that must be understood simultaneously:

NO as a CCO inhibitor - a problem that light resolves
Under conditions of oxidative stress or reduced oxygen flow, NO binds to cytochrome c oxidase and blocks its function. Mitochondria produce less ATP, and cells enter an energy deficit. Red and NIR light dissolve this blockage - NO is released and CCO resumes normal function. This is the primary mechanism through which photobiomodulation restores mitochondrial function under oxidative stress conditions.

Released NO as an active therapeutic molecule
Released NO is not just a byproduct - it actively functions as a vasodilator, anti-inflammatory mediator, and neuroprotective molecule. Local vasodilation after red light therapy improves circulation in the treated tissue, which can have a cascading effect on the regeneration of distant areas through improved blood supply.

A review published in the journal Nitric Oxide (Kashiwagi et al., 2023, Massachusetts General Hospital) evaluates photobiomodulation as a promising strategy for restoring endothelial function in cardiovascular diseases precisely through the mechanism of increasing NO bioavailability. [R]

Related terms

• Photobiomodulation - therapy using red and NIR light that directly stimulates the release of NO
• Mitochondria - organelles in which NO is bound to CCO and from which light releases it
• ATP - cellular energy; its production increases after NO is released from CCO
• Cytochrome C oxidase (CCO) - an enzyme of the respiratory chain to which NO binds and inhibits; light breaks this bond
• Vasodilation - widening of blood vessels caused by NO; improves microcirculation and blood flow
• Endothelium - the inner lining of blood vessels where eNOS operates and NO is produced to regulate vascular tone
• NOS (NO synthase) - enzymes catalyzing the enzymatic synthesis of NO from L-arginine; three isoforms: eNOS, nNOS, iNOS
• Oxidative stress - a state of excessive production of reactive oxygen species, in which NO binding to CCO is most pronounced
• NIR - near-infrared light; together with the red spectrum, it releases NO from both mitochondrial and blood reservoirs
• Pulsation and nitric oxide - pulsed mode affects NO binding and release patterns differently than continuous light

Frequently asked questions about nitric oxide

What is nitric oxide and why is it important?

Nitric oxide (NO) is a gaseous signaling molecule produced directly in the human body - it is not a toxic gas from the environment. The body produces it enzymatically from the amino acid L-arginine and uses it to dilate blood vessels, regulate blood pressure, support anti-inflammatory processes, promote wound healing, and regulate cellular energy metabolism. It is one of the most important signaling molecules in the body and the subject of a Nobel Prize-winning discovery.

What is the relationship between red light and nitric oxide?

Red and near-infrared light release NO through two mechanisms: first, they break the bond between NO and cytochrome c oxidase in mitochondria - which simultaneously unblocks CCO and increases ATP production. Second, they release NO from blood reservoirs (nitrosylhemoglobin, S-nitrosothiols) - this mechanism is independent of NOS enzymes. The result is local vasodilation, increased blood flow, and a cascade of anti-inflammatory and regenerative signals.

How long does vasodilation last after red light therapy?

According to a clinical study from 2022 (Medical College of Wisconsin), blood flow in the treated tissue remained statistically significantly elevated for 30 minutes after the end of a 5 to 10-minute exposure to 670 nm light at an intensity of 50 mW/cm². The duration of vasodilation depends on the light dose and the condition of the vascular endothelium.

Can I increase NO production through diet?

Yes. Intake of foods rich in nitrates (leafy greens: spinach, arugula, beetroot) and the amino acid L-arginine (pumpkin seeds, walnuts, turkey meat) supports the enzymatic synthesis of NO. Physical activity also increases eNOS production in the endothelium. Red and near-infrared light therapy acts as a complementary mechanism — it releases NO from existing reservoirs and improves the availability of biologically active NO independently of diet.

Is nitric oxide the same as nitrogen dioxide (NO₂)?

No. They are two chemically distinct molecules with completely different properties. Nitric oxide (NO) is a biological signaling messenger produced by the body, beneficial at appropriate concentrations. Nitrogen dioxide (NO₂) is an atmospheric pollutant from combustion engines that irritates the respiratory tract when inhaled. In the context of photobiomodulation and health, we are referring exclusively to nitric oxide (NO).

Can nitric oxide also be harmful?

Like most biological molecules, NO has a biphasic effect - it depends on concentration and context. At physiological concentrations (produced via eNOS), NO has protective effects. At excessive concentrations (produced by iNOS during chronic inflammation), it can react with reactive oxygen species to form peroxynitrite, which is cytotoxic. Red light therapy operates within the biological range where the effects of NO are clearly beneficial — not within the pathological range of chronic inflammation.

Why is nitric oxide also mentioned in grounding and earthing?

Grounding (contact of bare feet with the earth) also modulates NO levels in the body - likely through normalization of cellular redox potential and reduction of oxidative stress. The combination of grounding, sunlight, and red light therapy forms the foundation of the Mitochondriak® approach to naturally optimizing NO production. Learn more about this synergy in the article Grounding, light, and more efficient ATP production.

Summary

Nitric oxide (NO) is a gaseous signaling molecule produced by the vascular endothelium and mitochondria, which dilates blood vessels, releases the mitochondrial enzyme cytochrome c oxidase, increases the production of ATP, reduces inflammation, and protects tissues from ischemia. Red and near-infrared light (especially wavelengths of 630 nm, 670 nm, and 850 nm) measurably releases NO from both mitochondrial and blood reservoirs - this is one of the key mechanisms through which photobiomodulation acts on the human body.

Learn more about the mechanisms of red light therapy in the section Studies and benefits of red light therapy or explore our Mitochondriak® devices.

Scientific studies and sources

• Kashiwagi S et al. Photobiomodulation and nitric oxide signaling. Nitric Oxide. 2023. Massachusetts General Hospital / Harvard Medical School. PMC9808891
• Keszler A et al. In vivo characterization of a red light-activated vasodilation - 670 nm, blood flow increased 30 minutes after exposure. Frontiers in Physiology. 2022. PMC9108481
• In vivo measurement of NO release from intact human skin post photobiomodulation - 660 nm and 850 nm, 18 healthy participants. Journal of Photochemistry and Photobiology. 2024. doi.org/10.1016/j.jpap.2024
• Hamblin MR. Mechanisms and mitochondrial redox signaling in photobiomodulation - CCO, NO, ATP. Photochem Photobiol. 2018. PMC5844808