Citrulline

Citrulline is a non-protein amino acid produced by humans in the liver and intestine, and found in foods such as watermelon (“Citrullus” in Latin). The urea cycle in our cells converts citrulline to arginine, a protein amino acid, and vice-versa.

Citrulline is an intermediate in metabolic pathways, including the urea cycle (removing nitrogen from protein in the urine) and in nitric oxide synthesis. Providing citrulline increases both arginine and nitric oxide, both of which have potential benefits.

Citrulline can be made by our bodies and deficiency is unknown outside of rare metabolic conditions.

Nitric oxide has a critical role in regulating blood flow. Citrulline supplementation increases nitric oxide levels, which increases blood flow throughout the body. Increased blood flow potentially improves heart function, decreases blood pressure, increases exercise capacity, assists in muscle building, and reduces symptoms of erectile dysfunction (ED). Citrulline may also improve cognition and mood by improving brain blood flow.
Citrulline supplementation is best known in terms of its potential effects in athletic performance. Several studies have shown that citrulline may improve athletic performance [for review: https://pubmed.ncbi.nlm.nih.gov/31977835], particularly endurance, by increasing blood flow and thus the amount of oxygen in muscle tissue. One study found that men who took citrulline were able to do 50% more weight training repetitions than those on placebo. In another controlled study, cyclers biked 4 km faster with less fatigue on citrulline [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4759860]. Many studies used 2.5-3 grams of citrulline. Note that the combined citrulline plus arginine content of ActivNeeds is 3 grams.

Citrulline, like other amino acids, can cause gastrointestinal issues such as bloating, cramping, or diarrhea. However, side effects are unlikely in the moderate dosing (2 grams) present in ActivNeeds®. Although no known side effects have been reported with doses of at least 10 grams, discuss with your physician if you are on medication for erectile dysfunction, high blood pressure, or angina, as there may be medication interactions. Side effects are unexpected at the doses used in ActivNeeds.

Laboratory testing can test for citrulline, but is generally not likely to have clinically utility.