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Nitric Oxide

Nitric oxide (NO) is composed of nitrogen (N) and oxygen (O). The human body creates NO from dietary arginine and nitrate. NO plays a major signaling role in vascular relaxation, and elevated levels are associated with better blood flow and lower blood pressure.

Our evidence-based analysis on nitric oxide features 31 unique references to scientific papers.

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Summary of Nitric Oxide

Overview | How are nitric oxide levels assessed? | What affects nitric oxide levels?

Overview

The human body converts nitrate to nitric oxide (NO), which is a signaling molecule associated with several physiological functions involving blood pressure regulation, cardiovascular health, mitochondria production, calcium transport, oxidative stress, and skeletal muscle repair.[1] It plays a prominent role as a vasodilator, which means it relaxes blood vessels and improves blood flow.

Nitrate supplementation, whether in its pure form (e.g. sodium/potassium nitrate), or via foods (e.g. beetroot juice/powder), may temporarily reduce the body’s oxygen demand during exercise. A decrease in oxygen demand may result in improved exercise and muscular performance.[2][3]

How are nitric oxide levels assessed?

Direct

The most accurate method of assessing NO levels is to measure plasma nitrate and nitrite in your blood. The half-life of NO is incredibly short, existing for less than 0.1 seconds before it breaks down into nitrate and nitrite.[4][5] These two metabolites are measured as stand-in measures (i.e., surrogate markers) of NO production.

Researchers may not use this method due to inconvenience or cost concerns. Instead, they may opt to use indirect approaches.

Indirect

It is not uncommon for researchers to test the effects of a nitrate-rich supplement on secondary endpoints affected by NO levels. Below is a list of frequently used endpoints.

Blood pressure

Heart stroke volume

Speed

Cardiac output

Max effort

Strength

Erections

Muscle oxygenation

Time trials

Graded exercise tests

Open-ended exercise tests

VO2max

Heart rate

Power output

VO2peak

What affects nitric oxide levels?

Supplements

NO levels can be increased through direct nitrate ingestion. Obvious, right? But there’s a twist — nitrates do not exist as isolated dietary supplements due to the regulations surrounding high quantities of sodium nitrate. Instead, nitrate supplementation is typically achieved via nitrate-rich foods or beverages. Most studies deliver nitrates in the form of beetroot juice or powder.

Supplements like citrulline and arginine may also boost NO levels, but their overall effect is moderate to minor.[6] Plant isoflavones, such as soy isoflavones, may also influence NO production.

The table below displays an analysis of human studies and indicates how supplements may affect NO levels and production.

Food

Nitrates are found in various foods, notably beetroot and leafy green vegetables. Beetroot extract capsules do not provide enough nitrates to affect blood flow, but beetroot powder and juice are valid options.

Arugula/rocket, collard greens, dill, and turnip greens also have a high nitrate content.[7][8]

Hormones

Estrogen regulates blood flow by inducing the production of NO,[9] a potent vasodilator made by endothelial cells, which is a specialized cell type lining all blood vessels. After being produced in the endothelium, NO diffuses into the underlying smooth muscle cells that regulate vascular tone, causing them to relax and subsequently increase blood flow through the body. This process is called vasodilation.

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Human Effect Matrix

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The Human Effect Matrix looks at human studies to tell you what supplements affect Nitric Oxide.

Full details on all Nitric Oxide supplements are available to Examine members.
Grade Level of Evidence
Robust research conducted with repeated double-blind clinical trials
Multiple studies where at least two are double-blind and placebo controlled
Single double-blind study or multiple cohort studies
Uncontrolled or observational studies only
Level of Evidence
? The amount of high quality evidence. The more evidence, the more we can trust the results.
Supplement Magnitude of effect
? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
Notes
grade-b Minor High See all 7 studies
Has been implicated in increasing nitric oxide formation in the body, but this does not appear to be a reliably occurring phenomena (despite arginine being required to make nitric oxide, it is not a good inducer thereof)
grade-c Notable Very High See 2 studies
Nitric oxide derivatives (nitrate and urinary cGMP, since nitric oxide itself is hard to measure these biomarkers are indicative of nitric oxide production) appear to be reliably increased following oral consumption of citrulline supplementation
grade-c Notable - See study
80mg of a bioavailability enhanced curcumin supplement has been reported to increase nitric oxide in serum by 40% or so, which is significantly larger than many other dietary supplements.

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Things to Note

Also Known As

NO

Click here to see all 31 references.