L-Citrulline is not a nitrate. The confusion arises because both L-Citrulline and inorganic nitrates are widely used as precursors to increase the body’s production of nitric oxide (NO). L-Citrulline is classified as a non-essential amino acid, a type of organic compound, while a nitrate is an inorganic salt. Although they share the goal of enhancing nitric oxide levels, they are fundamentally different in their chemical structure, origin, and the specific biological pathways they use.
Defining L-Citrulline
L-Citrulline is a non-essential amino acid that the human body can produce, primarily in the intestines and liver. Unlike the amino acids that form the building blocks of protein, citrulline does not participate in protein synthesis. Its name is derived from Citrullus vulgaris, the Latin name for watermelon, a food where it is found in high concentrations. This organic compound plays a role as a metabolic intermediate in the urea cycle, a process that helps the body safely excrete ammonia. Its structure, characterized by an amino group and a carboxylic acid group, makes it chemically distinct from the simple polyatomic ion that defines a nitrate.
Understanding Inorganic Nitrates
Inorganic nitrates are simple salts containing the nitrate ion (\(\text{NO}_3^-\)). This structure is fundamentally inorganic, lacking the carbon-hydrogen backbone that defines organic molecules like amino acids. Nitrates are highly water-soluble and occur naturally in the environment as part of the nitrogen cycle. These compounds are found in high concentrations in certain vegetables, such as spinach, beetroot, and arugula, and are often consumed via concentrated juices or supplements. Nitrates are classified as dietary components that serve as a substrate for a specific, non-enzymatic pathway for nitric oxide production.
Two Separate Routes to Nitric Oxide
The reason L-Citrulline and nitrates are often grouped is their shared ability to increase the bioavailability of nitric oxide, but they use two entirely separate biochemical mechanisms.
The L-Citrulline Pathway
The L-Citrulline pathway relies on a recycling loop involving L-Arginine. The enzyme nitric oxide synthase (NOS) converts L-Arginine into nitric oxide and L-Citrulline. The newly formed L-Citrulline is then recycled, primarily in the kidneys, back into L-Arginine, ensuring a sustained supply of the substrate for NOS. This L-Arginine/Nitric Oxide Synthase pathway is effective because L-Citrulline supplementation bypasses the extensive first-pass metabolism that rapidly breaks down L-Arginine in the gut and liver.
The Nitrate Pathway
Conversely, the nitrate pathway, known as the Entero-Salivary Circulation, is entirely independent of the NOS enzyme system. When dietary inorganic nitrate (\(\text{NO}_3^-\)) is consumed, it is absorbed into the bloodstream, and about 25% is concentrated in the saliva. Commensal bacteria on the back of the tongue use nitrate reductase enzymes to convert the nitrate into nitrite (\(\text{NO}_2^-\)). This nitrite is then swallowed, and under the acidic conditions of the stomach, it is converted into active nitric oxide. This mechanism is sensitive to the oral microbiome, meaning the use of antibacterial mouthwash can significantly disrupt the initial conversion of nitrate to nitrite, impairing the nitric oxide-boosting effect.
Why the Distinction Matters to the Consumer
The distinction between the two compounds is important for selecting the most appropriate supplement. The L-Citrulline pathway provides a sustained increase in L-Arginine, often preferred for maintaining consistently high nitric oxide levels over several hours for exercise performance and cardiovascular support. Conversely, the nitrate pathway offers a more rapid spike in nitric oxide, but its efficacy depends on a healthy oral microbiome. Consumers who frequently use antibacterial mouthwash may find nitrate supplements less effective due to the disruption of the necessary bacterial conversion. Some products, such as Citrulline Nitrate, combine the two to leverage both the Arginine/NOS and Entero-Salivary pathways simultaneously.