L-citrulline side effects

The clearest human safety data on L-citrulline comes from a single-dose escalation study that found no side effects at doses up to 15 g in 8 healthy men. The one side effect reported anywhere in the trials covered here is stomach discomfort, in about 15% of participants taking a single 8 g dose of citrulline malate before exercise.

What the dose-finding study found

A 2008 study gave 8 healthy men single oral doses of 2 g, 5 g, 10 g and 15 g of L-citrulline on separate days and monitored them for 8 hours. None of the men experienced side effects at any of the four doses. That's a small sample and a single-dose exposure rather than weeks of daily use, but it's the most direct human tolerability data available for plain L-citrulline.

The one side effect actually reported

A 2010 trial gave 41 men a single 8 g dose of citrulline malate before a bench-press training session. The only side effect reported was a feeling of stomach discomfort, in 14.6% of participants. Whether that's specific to the malate portion, the dose size, or taking it close to intense exercise isn't something the trial was designed to separate out — the plain-citrulline dose-finding study above, using higher doses without malate, reported no side effects at all.

What longer-term daily use looks like

A 2011 trial had 24 men take 1.5 g/day of L-citrulline for a full month and reported no adverse events. A 2025 trial running 6 weeks at higher daily doses (8 g plain citrulline or 12 g citrulline malate) reported on performance and blood-marker outcomes but didn't report a separate tally of side effects or dropouts in its published results — an absence of data, not a clean bill of health at that higher, longer-term dose.

Why more isn't assumed to be better

The 2008 dose-finding study found that at the two highest doses tested (10 g and 15 g), the rise in blood arginine was smaller than expected relative to the citrulline dose given — the researchers attributed this to the kidneys' conversion of citrulline to arginine becoming saturated at high doses. That's a reason to expect diminishing returns at higher doses, not a specific toxicity finding, since no side effects were reported even at 15 g in that trial.

Who has a more specific reason for caution

Some groups have a more specific reason to check with a doctor before using L-citrulline than the general population described above — see who should not take L-citrulline, and L-citrulline and medications: what to check if you take a regular prescription.

What to do if something feels wrong

Given how little dedicated tolerability data exists for this ingredient, a new or unexplained symptom after starting L-citrulline — digestive upset that doesn't settle, a rash, or anything else out of the ordinary — is a reason to stop and check with a doctor rather than assume it's unrelated.

Questions people ask

What are the side effects of L-citrulline?

The clearest data point comes from a dose-finding study that found no side effects at doses up to 15 g in a single sitting. The one side effect reported in any trial covered here is stomach discomfort, in about 15% of participants taking a single 8 g dose of citrulline malate before exercise.

Is L-citrulline safe?

The available human data — a single-dose safety study up to 15 g, a month of daily use at 1.5 g, and a 6-week trial at 8-12 g daily — hasn't turned up a specific safety signal, but none of these trials is large, and none ran longer than 6 weeks.

Does L-citrulline cause stomach problems?

One trial reported stomach discomfort in about 15% of participants after a single 8 g dose of citrulline malate; a separate trial using higher doses of plain citrulline, without malate, reported none — so it isn't clear whether the malate portion, the dose, or the exercise context was the reason.

Does L-citrulline cause headaches?

We didn't find a trial reporting headache as a side effect of L-citrulline specifically.