Meta analysis finds only lukewarm support for use of citrulline as aerobic performance enhancer

By Hank Schultz

- Last updated on GMT

©Getty Images - saintho
©Getty Images - saintho

Related tags Sports & Active Nutrition Summit USA Sports nutrition Sports nutrition sector Sports nutrition products citrulline Amino acid

It has been more than a century since citrulline has been identified and codified as a standalone amino acid. Even after all that time research on whether the ingredient provides a true aerobic performance benefit is mixed at best, a new review has found.

The new systematic review and meta analysis was published in late August in the journal Nutrients.​  It was the work of researchers associated with various universities and research institutes in Spain.

Citrulline is an amino acid found most abundantly in watermelon, from which it was first isolated by Japanese chemists in 1914. The amino acid, along with arginine, is a factor in the production of nitric oxide. 

The Spanish researchers noted the close interplay between the amino acids arginine and citrulline, but said that because citrulline is not broken down in the liver, the theory has been that it would boost NO production to a greater degree than would arginine, hence the interest in it as a performance ingredient. (Higher NO levels are thought to confer a benefit via greater blood flow.)

The researchers said that the performance enhancements that might be expected from citrulline supplementation were only ever modest at best, but noted that, “In competitive sport, a 1–2% improvement in performance can make the difference between winning and losing a competition and is, therefore, a critical difference.”

Criteria exclude most of research conducted so far

To find appropriate studies to review, the researchers used a net sized to capture papers that were:

  • Conducted on humans
  • Studies using a RCT methodology
  • Studies using a variety of active subjects, including competitive athletes, and including both men and women
  • Those with efforts of five minutes or more (thus excluding studies looking at short burst, peak power efforts)
  • Those that had well defined dosages and avoided the use of additional ergogenic aids, focusing on citrulline alone.

The researchers looked at more than 100 papers to start, but ended up with only 10 studies that met their standards for review.  The first of these studies was published in 2006, while the rest were published from 2014 to 2019.  The 10 studies included a total of 173 subjects.

Half of the studies used acute doses of citrulline administered from one hour to three hours before the test event.  The others used longer term supplementation, ranging from one day to 14 days.  

In all cases, the dosages were absolute and were not keyed to body weight, as is the case for the research into many other dietary ingredients.  The dosages ranged from a low of 1 gram/day to a high of 12 grams in a study in which a single dose was ingested one hour before the test. The average dose ranged from 3.4 grams  to 6 grams. 

Modest trend toward benefit was highest effect observed

The meta analysis looked at the effects observed on aerobic performance, rate of perceived exertion (RPE), VO2 kinetics and changes in blood lactate thresholds.  Even though some of the studies reviewed here had hopeful titles such as “Oral l-citrulline supplementation enhances cycling time trial performance in healthy trained men​,​” the Spanish researchers concluded that overall the best that could be said is that the chronic supplementation studies appeared to show a trend of benefit, whereas the studies using acute dosages did not.  

“This systematic review and meta-analysis has shown no significant positive effects of Cit supplementation on the different variables analyzed in relation to aerobic sports performance. Chronic supplementation (6–16 days) with an amount between 3.4 and 6 g/day showed a positive tendency to improve aerobic performance, but without statistical significance. Acute supplementation (1–3 h) with 1–12 g of Cit did not significantly improve aerobic performance or any related variables. No improvement in VO2 kinetics or the RPE was observed after Cit supplementation, irrespective of doses and timing,”​ the researchers wrote.

Results mirror ISSN position paper

The results of the meta analysis closely mirror what the International Society of Sports Nutrition had to say about citrulline in its most recent position paper on that ingredient and a number of others​.  The paper dates from 2018 and cites some of the same research as the Spanish study does.  The ISSN position paper, in reporting on the equivocal research, also noted that many studies used a citrulline malate form of the amino acid, with the physiological role the malate might play undefined.

2022, 14​(17), 3479;
Effects of Citrulline Supplementation on Different Aerobic Exercise Performance Outcomes: A Systematic Review and Meta-Analysis
Authors: Viribay A, et al.

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