Nitric oxide (NO) is recognized as a signaling molecule of life due to its critical roles in various physiological processes.

1. Vasodilation: Nitric oxide plays a role in dilating blood vessels. NO produced in vascular endothelial cells relaxes vascular smooth muscles, expanding blood vessels, regulating blood pressure, and improving blood flow. This is crucial for cardiovascular health.
2. Neurotransmission: NO acts as a neurotransmitter, aiding signal transmission between nerve cells. It plays a significant role in the brain and autonomic nervous system, contributing to memory, learning, and neural plasticity, which are essential for brain function.
3. Immune Response: NO is produced by immune cells to help fight pathogens. Immune cells like macrophages generate NO to kill bacteria and viruses.
4. Cellular Signaling: NO is involved in various cellular signaling pathways, regulating physiological responses such as cell growth, differentiation, and apoptosis, which impact critical life processes.
5. Oxidative Stress Regulation: NO helps regulate oxidative stress through its antioxidant properties, preventing cell damage and slowing aging.
6. Cardiovascular Health: NO plays a vital role in preventing and treating cardiovascular diseases. A deficiency in NO is associated with conditions like hypertension, atherosclerosis, and myocardial infarction.

Due to these roles, NO is recognized as a key signaling molecule in various physiological processes. In 1998, Robert F. Furchgott, Louis J. Ignarro, and Ferid Murad were awarded the Nobel Prize in Physiology or Medicine for their discoveries regarding the physiological significance of NO.

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Since the Nobel Prize, numerous studies spanning generations have been conducted to increase NO levels in the human body.First-Generation Nitric Oxide Supplement: Arginine SupplementArginine aids in producing NO by combining with nitric oxide synthase (NOS) in the body.Advantages:

• Helps produce deficient nitric oxide.Disadvantages:
• Absorption rate decreases with high doses.
• Prolonged use reduces NOS efficiency, leading to decreased NO production.
• May accumulate in blood vessels, increasing the risk of atherosclerosis.

Second-Generation Nitric Oxide Supplement: Citrulline SupplementCitrulline is converted into arginine in the body, promoting NO production.Advantages:

• Higher absorption rate and longer duration compared to arginine supplements.Disadvantages:
• As a precursor to arginine, it inherits arginine’s drawbacks.

Third-Generation Nitric Oxide Supplement: Beetroot Supplement, Nitrate SupplementBeetroot is rich in nitrates, which are converted into NO in the body. Nitrate supplements provide nitrates directly for NO conversion.Advantages:

• Natural nitrates have minimal side effects.Disadvantages:
• The amount converted to NO is minimal, making it ineffective for significantly increasing NO levels.

Fourth-Generation Nitric Oxide Supplement (HumanNOS): NO Metabolites + Antioxidant MetabolitesArginine, citrulline, and nitrates are all NO precursors. Their intake requires metabolism through the body’s organs and enzymes, contributing to energy consumption and inefficient NO production. HumanNOS’s nitric oxide is a metabolite that overcomes these shortcomings and is efficiently absorbed by cells.Advantages:

• Metabolites allow efficient cellular absorption.
• Does not accumulate in the body and is fully excreted.
• NO levels can be controlled through dosing.
• Provides not only NO but also essential antioxidant nutrients as metabolites.
• No side effects.

There are three main ways to naturally produce nitric oxide.

1. Sunlight: Ultraviolet (UV) A rays from sunlight can promote the release of nitric oxide by converting nitrates stored in the skin. However, excessive UV exposure carries risks su
2. Exercise: Exercise promotes nitric oxide production and release, improving blood flow and aiding in the delivery of oxygen and nutrients to muscles.
3. Diet: Consuming foods rich in L-arginine (e.g., meat, legumes, nuts) and nitrates (e.g., beets, spinach) promotes nitric oxide production.

While a healthy lifestyle and diet can support nitric oxide supplementation, they have limitations in producing sufficient nitric oxide. Taking safe and effective nitric oxide supplements is important.

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L-Arginine and L-citrulline, as precursors to NO, help produce NO by combining with nitric oxide synthase (eNOS) in the body when ingested. However, the efficiency of eNOS decreases with age, so even consuming large amounts of precursors cannot produce sufficient NO. Therefore, it is appropriate to consume NO in the form of metabolites rather than precursors.

• Effective cases: Can aid NO production in individuals in their 10s to 20s with healthy eNOS.
• Ineffective cases: Effects are minimal when there is a defect in vascular endothelial cells or reduced eNOS efficiency.
• Disadvantages: As precursors, L-arginine and L-citrulline require bodily metabolism, consuming enzymes and energy, and may accumulate in the body, potentially causing atherosclerosis.

The reasons why nitric oxide (NO) production and availability decrease with age are as follows:

• Decline in endothelial function: The function of vascular endothelial cells declines, reducing the activity of NO synthase.
• Increased oxidative stress: An increase in reactive oxygen species (ROS) reduces NO availability.
• Weakened antioxidant system: Decreased antioxidant levels in the body reduce defenses against ROS and NO stability.
• Reduced nutrient absorption: Aging of metabolic organs reduces efficient nutrient uptake, leading to a decrease in essential amino acids needed for NO synthesis.

A decrease in nitric oxide leads to the decline of various protective functions in the body:

• Cardiovascular decline
• Hypertension
• Atherosclerosis
• Cardiovascular diseases (stroke, myocardial infarction, etc.)
• Neurological decline
• Cognitive impairment
• Neurodegenerative diseases
• Immune function decline
• Autoimmune diseases
• Reduced recovery capacity
• Muscle function decline
• Decreased exercise capacity
• Reduced muscle recovery