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L-Citrulline Overview


Some shipments of L-citrulline, an amino acid supplement used to treat genetic disorders in children, can cause serious harm and in some cases could lead to death.

L-citrulline is a dietary supplement that increases levels of citrulline in the body. Citrulline, an amino acid, occurs naturally and aids in the body's urea cycle, the process that clears ammonia – a byproduct of normal metabolism – out of one’s system.

Physicians can prescribe these supplements -- sold as tablets, capsules, liquids and powders – to help treat certain genetic disorders and a variety of other illnesses. Without a prescription, consumers can take over-the-counter versions of the supplements. The most common over-the-counter users today are bodybuilders and athletes who want to boost their endurance.

Other purported benefits include increased energy, enhanced circulation and improved immune system function. Scientific evidence to either confirm or refute these claims is lacking, with the few small studies that have been done producing conflicting results.

Treatment for certain urea cycle disorders is arguably the most important use of L-citrulline. These rare conditions cause a deficiency of enzymes, mostly in children. Because these enzymes remove ammonia from the bloodstream, a lack of them can cause a buildup of ammonia. Untreated, this buildup can lead to brain damage, coma and death.

Several shipments of L-citrulline were recalled in early 2014 because they contained the wrong ingredient. Those stocks endangered children with urea cycle disorders who depend on the supplement.

Common Uses

Medical experts assign L-citrulline supplements for:
Certain genetic disorders Erectile dysfunction
Alzheimer's disease Dementia
High blood pressure Cardiovascular disease
Sickle cell anemia Lysinuric protein intolerance
Reye's syndrome

Doctors sometimes prescribe the supplements after heart surgery to prevent pulmonary hypertension. In those instances, they are given intravenously. Many of these uses are supported by some clinical evidence, but in most cases more research is needed to prove any conclusive benefits.

Possible Side Effects and Interactions

Because citrulline is created by the body, L-citrulline supplements are generally believed to be safe. Side effects are rare with the use of either pharmaceutical-grade or over-the-counter supplements. However, doctors advise women who are pregnant or nursing to avoid taking them. Scientific evidence about the supplements’ safety for women in these conditions is lacking.

L-citrulline may interact with some prescription drugs, including certain medications used to treat hypertension, cardiovascular disease and erectile dysfunction. Individuals who take medications regularly, either prescription or over-the-counter, should consult a health care professional before taking L-citrulline.

Bad Lots Spur Recall

In February 2014, some pharmaceutical-grade L-citrulline supplements were recalled. Medisca Inc., a Plattsburg, N.Y.- based compounding firm, issued a voluntary recall of eight defective lots of its L-citrulline products, which are distributed to hospitals and pharmacies nationwide. According to a safety alert released by the FDA, these bad lots were found to contain no L-citrulline at all.

Instead, FDA lab testing found that they contained N-acetyl-leucine, a drug used in the treatment of vertigo. Adverse reactions, some of them serious, have been reported in a number of children treated with these mislabeled supplements.

The FDA advises health care professionals, caregivers and patients that Medisca L-citrulline products with the following lot numbers should not be used:

  • 95482/A
  • 95482/B
  • 95482/C
  • 95482/D
  • 96453/A
  • 96453/B
  • 96453/C
  • 96453/D

Additionally, patients using L-citrulline who have concerns should contact their health care provider, and any adverse reactions or quality problems should be reported to MedWatch, the FDA's safety information and adverse event reporting program.