Determination of Variances in Exhaled Nitric Oxide Output in Normal Healthy Male Volunteers Consuming High and Low Nitrate/Nitrite Diets

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00027157
Recruitment Status : Completed
First Posted : November 28, 2001
Last Update Posted : March 4, 2008
Information provided by:
National Institutes of Health Clinical Center (CC)

Brief Summary:

This study will determine whether and how nitrites and nitrates in the diet affect the level of nitric oxide gas that is breathed out in air. Nitric oxide is involved in many bodily processes, such as immune function, nerve signal transmission, inflammation, and dilation of blood vessels and bronchial tubes (tubes that branch out from the trachea into the lungs).

Healthy male volunteers age 18 years or older who have not smoked for at least 5 years may be eligible for this study. Candidates will undergo blood and urine tests, breathing tests, and an electrocardiogram.

Participants will follow two special diets for 3 days each. One is a low-nitrate and nitrite diet, and the other is a high-nitrate and nitrite diet. Both diets must be completed within a month's time. Participants will be admitted to the NIH Clinical Center for two 3-night hospital stays during the two diet periods, but may go out on passes at any time. While on the diets, they may consume only food prepared by the NIH Nutrition Department; eating other foods will seriously affect the study results. Meals may be eaten at the NIH Clinical Center, or packaged meals prepared by the Nutrition Department can be taken out. Participants may not engage in any heavy exercise during the diet periods, as exercise affects nitric oxide levels.

Blood samples of about 4 milliliters, or 1 teaspoon, each will be collected before starting each diet and at the end of each diet to measure blood levels of nitrate and nitrite. Additional blood samples, totaling about 2 tablespoons, will be collected for research. Each day, participants will have a test to measure exhaled nitric oxide levels. This involves blowing air into a mouthpiece attached to a machine that measures levels of the gas in each breath.

Condition or disease

Detailed Description:

Nitric oxide (NO) has been recognized for its multifaceted roles in many physiological processes (e.g., vasodilatation, host defense, neurotransmission, bronchodilatation, and inflammation.) NO is produced by a family of nitric oxide synthase (NOS) isoforms in a reaction that converts L-arginine to L-citrulline. NO metabolites in vivo include nitrite (NO2) and nitrate (NO3). Plasma NO2/NO3 concentrations have been used extensively as a marker for NOS activity and NO radical production. Studies have shown that dietary intake of nitrate, estrogen, atmospheric pollution, and heavy exercise can influence NO2/NO3 levels in blood. NO can also be detected in exhaled air. NO levels vary with disease, and in some cases (e.g., asthma) respond to treatment (e.g., steroid).

This pilot study is designed to determine whether or not dietary intake influences exhaled NO levels. To use plasma metabolite measurements to monitor NOS activity, subjects must adhere to a strict low NO2/NO3 diet before and during the study where measurements of exhaled NO can be performed quickly and easily in an inpatient setting. Subjects will be studied as inpatients consuming standardized high and low nitrite/nitrate (NO2/NO3) diets each for a period of three days. Since L-arginine is a NOS substrate and can affect the generation of NO, diets will also be monitored by protein intake. Blood samples will be collected four times during the study, pre- and post-diet for each diet, for the quantification of NO2/NO3 concentration. Exhaled NO will be measured daily. In addition, blood pressure, pulmonary function testing, and blood plasma levels of L-arginine, cyclic guanosine monophosphate (cGMP), and S-thiolation may be monitored. Results of this study should allow us to determine the most effective method of monitoring NOS activity, and potentially identify activities responsible for maintaining nitric oxide levels.

Study Type : Observational
Enrollment : 18 participants
Official Title: The Determination of Variances in Exhaled Nitric Oxide Output in Normal Healthy Male Volunteers Consuming High and Low Nitrate/Nitrite Diets
Study Start Date : April 2000
Study Completion Date : April 2003

Resource links provided by the National Library of Medicine

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes


Inclusion criteria for research volunteers include (1) male; (2) good overall health history without any recent (3 months) acute disease; (3) physical examination within normal limits; (4) laboratory evaluation; including complete blood count (CBC), acute care panel, clotting times, chest x-ray (only if medically indicated), pulmonary function testing and an electrocardiogram (EKG)-within normal limits; (5) non-smokers defined as having never smoked or not smoked within the past 5 or more years; (6) willingness to commit to the three day strict low NO(2)/NO(3) diet and three day high NO(2)/NO(3) diet prepared by the Nutrition Department and supplied as either hot meals or pre-packaged meals; and (7) willingness to avoid intensive exercise, e.g., running, jogging, aerobics, etc., during the entire study.


Exclusion criteria include (1) age less than 18; (2) females; (3) positive serum test for hepatitis virus; and (4) inability to complete reliable pulmonary function tests.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00027157

United States, Maryland
National Heart, Lung and Blood Institute (NHLBI)
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Heart, Lung, and Blood Institute (NHLBI)

Publications: Identifier: NCT00027157     History of Changes
Other Study ID Numbers: 000118
First Posted: November 28, 2001    Key Record Dates
Last Update Posted: March 4, 2008
Last Verified: April 2003

Keywords provided by National Institutes of Health Clinical Center (CC):
Coronary Spasm
Endothelial-Derived-Relaxation Factor
Nitric Oxide Synthase
Susceptibility Genes

Additional relevant MeSH terms:
Nitric Oxide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Free Radical Scavengers
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Vasodilator Agents
Protective Agents