L-Citrulline vs. L-Arginine: Which One Actually Raises Arginine?
It sounds backwards, but the best way to raise blood arginine may be to swallow citrulline. Here is the physiology and the human data behind that.
Two amino acids, one cycle
Arginine is the amino acid that nitric oxide synthase turns into nitric oxide, leaving citrulline behind. Citrulline can then be recycled back into arginine, both inside vessel cells and, on a larger scale, in the kidneys. The two are partners in a loop. A normal diet provides several grams of arginine a day, from protein foods; citrulline comes mostly from the body's own production in the gut, with watermelon as the main dietary source[3].
The arginase problem
When you swallow arginine, a sizeable share never reaches the general circulation. Arginase enzymes in the intestinal wall and the liver break it down to ornithine and urea first. This "first-pass" loss is one reason arginine supplements need gram doses, and one proposed piece of the "arginine paradox"[2].
What the human study showed
In a randomized, double-blind crossover study, 20 healthy volunteers took different doses of citrulline, arginine, both, or placebo for a week each. Citrulline raised plasma arginine in a dose-dependent way, and did so more efficiently than arginine itself; it also increased markers of nitric oxide signaling, such as urinary nitrate and cyclic GMP[1]. Reviews of citrulline's cardiometabolic research and of both amino acids for blood pressure draw the same conclusion[6][7].
Tolerance
Large single doses of arginine, around 9 grams or more, frequently cause nausea and diarrhea because unabsorbed arginine pulls water into the gut[5]. Citrulline was well tolerated at single doses up to 15 grams in the Citrudose study[4]. For anyone considering research-sized doses, citrulline is the gentler choice.
Side by side
| L-Citrulline | L-Arginine | |
|---|---|---|
| Broken down by gut and liver arginase | No | Yes, substantially |
| Raises plasma arginine | Efficiently | Less efficiently per gram |
| Typical research dose | 3-6 g/day | 4-24 g/day |
| Digestive tolerance at high dose | Good | Often poor above ~9 g |
| Main food source | Watermelon | Meat, fish, dairy, nuts, legumes |
What this means for blended products
Products that combine both, such as Melonex, which lists citrulline malate first in a 500 mg blend with two arginine forms, are making a reasonable bet on citrulline. The question that matters is dose: research effects came from grams, and a blend that does not state its amounts cannot be compared with that research. If you are choosing between products, a clearly labeled citrulline dose is more useful than a long ingredient list.
Bottom line
For raising arginine and nitric oxide signaling, oral citrulline beats oral arginine gram for gram, and it is easier on the stomach. Neither is a substitute for blood pressure treatment, and anyone on heart or blood pressure medicines should ask their clinician before taking either.
Sources for this page
Every entry links to the original record. The trials used single amino acids, usually at several grams a day; none of them tested the Melonex capsule.
- 1Schwedhelm E, Maas R, Freese R, et al. Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. Br J Clin Pharmacol. 2008;65(1):51-59. pubmed.ncbi.nlm.nih.gov/17662090/
- 2Boger RH. The pharmacodynamics of L-arginine. J Nutr. 2007;137(6 Suppl 2):1650S-1655S. pubmed.ncbi.nlm.nih.gov/17513442/
- 3Wu G, Meininger CJ. Arginine nutrition and cardiovascular function. J Nutr. 2000;130(11):2626-2629. pubmed.ncbi.nlm.nih.gov/11053497/
- 4Moinard C, Nicolis I, Neveux N, et al. Dose-ranging effects of citrulline administration on plasma amino acids and hormonal patterns in healthy subjects: the Citrudose pharmacokinetic study. Br J Nutr. 2008;99(4):855-862. pubmed.ncbi.nlm.nih.gov/17953788/
- 5Grimble GK. Adverse gastrointestinal effects of arginine and related amino acids. J Nutr. 2007;137(6 Suppl 2):1693S-1701S. pubmed.ncbi.nlm.nih.gov/17513449/
- 6Allerton TD, Proctor DN, Stephens JM, et al. L-Citrulline supplementation: impact on cardiometabolic health. Nutrients. 2018;10(7):921. pubmed.ncbi.nlm.nih.gov/30029482/
- 7Khalaf D, Kruger M, Wehland M, Infanger M, Grimm D. The effects of oral L-arginine and L-citrulline supplementation on blood pressure. Nutrients. 2019;11(7):1679. pubmed.ncbi.nlm.nih.gov/31336573/
Ready to run a fair 60-day Melonex trial?
Orders finish on the maker's BuyGoods checkout. Keep a morning blood pressure log, and if the numbers do not move, email support before day 60: opened and empty bottles both qualify.