L-Arginine vs L-Citrulline: Absorption, Nitric Oxide and What Trials Compared
L-arginine and L-citrulline compared: how each raises blood arginine, what blood pressure and exercise reviews found, a heart-attack trial warning, and who should ask a clinician.
Content last updated . This page has not been medically reviewed.
Quick answer
Arginine is an amino acid and a substrate of nitric oxide synthase, the enzyme that makes nitric oxide. [2] Nitric oxide is linked to blood vessel relaxation (vasodilation). [4] Citrulline is readily absorbed and at least in part converted to arginine. [4] The best-documented difference is in how they behave in the gut and blood: in one crossover study, oral citrulline raised blood arginine more than oral arginine did. [4] Whether that translates into better health or exercise results is much less clear. There is no universal winner, and no trial we read compared arginine and citrulline head to head for blood pressure or performance.
How the sources classify them
A review describes arginine and glutamine as conditionally essential amino acids, meaning the body can usually make enough but may fall short under stress or illness. [5] A review of exercise research describes citrulline as a nonessential amino acid found primarily in watermelon. [6] Neither is one of the nine essential amino acids; see Essential Amino Acids. Profiles of both are at L-Arginine and L-Citrulline.Evidence labels used below: physiology study means a short experiment on how the body handles an amount; mixed means studies disagree; promising but limited means small or short trials; evidence of harm in a specific group means a trial raised a safety signal.
What trials and reviews compared
| Question | What the source found | Evidence label |
|---|---|---|
| Raising blood arginine | In a placebo-controlled crossover study of 20 healthy volunteers, citrulline increased plasma arginine more effectively than arginine itself. [4] The authors point to extensive loss of arginine in the gut from intestinal arginase activity. [4] | Physiology study |
| Blood pressure, arginine | A meta-analysis of 11 placebo-controlled trials (387 people, study amounts of 4 to 24 g a day) found lower blood pressure than placebo. [2] | Promising but limited; published in 2011 |
| Blood pressure, citrulline | A 2019 meta-analysis of 8 trials suggested citrulline may reduce systolic pressure, with study sizes of 12 to 34 people. [3] A 2018 meta-analysis of five interventions found no beneficial effect on blood pressure. [7] | Mixed |
| Exercise performance, citrulline | A review reported evidence for acute improvements in blood flow after citrulline is scarce and inconsistent, though several studies reported citrulline can enhance exercise performance and recovery. [6] | Mixed |
| After a heart attack, arginine | Six deaths in the arginine group against none with placebo; enrollment was closed because of safety concerns. [1] | Evidence of harm in that group |
| Pre-eclampsia in pregnancy | A 2025 review found low-certainty evidence for arginine and only one small citrulline study (36 women) with no effect found. [8] | Insufficient evidence |
Proper evidence not found, in the sources we searched (PubMed for arginine versus citrulline trials on blood pressure, performance and nitric oxide), for a direct head-to-head trial showing one better than the other on a health outcome. A rise in blood arginine is a biomarker change, not a clinical outcome. For fuller evidence see Arginine, Citrulline, Nitric Oxide and Blood Pressure. Trials used supplements in specific amounts; those are study amounts, not advice.
Related
Amino Acids, Heart Disease and Blood Pressure · Amino Acids & ProteinFrequently asked questions
Is citrulline better than arginine?
Citrulline raised blood arginine more than arginine did in one small crossover study. [4] No source we read shows it works better for blood pressure or exercise.
Why is arginine absorbed poorly?
The study authors attribute it to extensive loss before it reaches the blood, because of arginase activity in the intestine. [4]
Do arginine and citrulline lower blood pressure?
Some meta-analyses found modest reductions and one found none. [2][3][7] Do not stop or change a prescribed medicine on this basis.
Is arginine safe after a heart attack?
One trial recommended against it in that setting. [1] Ask your cardiology team.
Are they safe in pregnancy?
A 2025 review called arginine findings low-certainty and said more trials are needed. [8] Decisions belong with your obstetric clinician.
More details: evidence, limits and cautions
The details behind this page: cautions, limits of the evidence and where sources disagree. Open any note to read it.
Quick safety note
People who have had a heart attack, who have heart disease, or who take medicines for blood pressure or heart conditions should talk to a clinician or pharmacist before using either supplement. In one randomized trial of people after a heart attack, 6 participants (8.6%) in the L-arginine group died during the six-month study, against none in the placebo group, and the authors concluded L-arginine should not be recommended after an acute heart attack. [1] That was a specific patient group and a specific study, not a finding about healthy people, but it is a reason to ask first. Both ingredients are studied for effects on blood pressure, and the reviews below show lower readings in some trials, so tell your pharmacist if you use blood pressure medicines. [2][3]
Side effects and safety
In a study of eight healthy men given single amounts of 2, 5, 10 or 15 g of citrulline, none had side effects, though at the highest amounts citrulline built up in plasma while arginine rose less than expected. [9] That was short-term and tiny. A 2008 risk assessment found no systematic pattern of adverse effects of oral arginine in human trials, so the usual method for setting a tolerable upper intake could not be used; that is not an official upper limit. [10] The sources we read give no official intake levels (RDA, AI or UL) for either compound, so none are stated here.
- Medicines: Proper evidence not found in the sources we read for specific interactions. Because both are studied for blood pressure effects, ask a pharmacist, especially if you use blood pressure medicines or nitrates. See How Interactions Work and Amino Acid Supplement and Medicine Interactions.
- Pregnancy, children, kidney and liver disease, surgery: supplements may carry risks if you have certain medical problems or are having surgery; tell your health care providers about all of them well before an operation. [11] Many have not been tested in pregnant women, nursing mothers or children. [11] See Amino Acid Supplements in Pregnancy, Children and Older Adults.
- Quality: see Quality Testing and Certifications.
References
- Schulman SP et al. L-arginine therapy in acute myocardial infarction: the VINTAGE MI randomized clinical trial. JAMA 2006. Read 2026-10-22.
- Dong JY et al. Effect of oral L-arginine supplementation on blood pressure: a meta-analysis of randomized, double-blind, placebo-controlled trials. Am Heart J 2011. Read 2026-10-22.
- Barkhidarian B et al. Effects of L-citrulline supplementation on blood pressure: a systematic review and meta-analysis. Avicenna J Phytomed 2019. Read 2026-10-22.
- Schwedhelm E et al. Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. Br J Clin Pharmacol 2008. Read 2026-10-22.
- Morris CR et al. Acquired amino acid deficiencies: a focus on arginine and glutamine. Nutr Clin Pract 2017. Read 2026-10-22.
- Gonzalez AM, Trexler ET. Effects of citrulline supplementation on exercise performance in humans: a review of the current literature. J Strength Cond Res 2020. Read 2026-10-22.
- Mirenayat MS et al. Effect of L-citrulline supplementation on blood pressure: a systematic review and meta-analysis of clinical trials. Curr Hypertens Rep 2018. Read 2026-10-22.
- Makama M et al. L-arginine and L-citrulline for prevention and treatment of pre-eclampsia: a systematic review and meta-analysis. BJOG 2025. Read 2026-10-22.
- Moinard C 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. Read 2026-10-22.
- Shao A, Hathcock JN. Risk assessment for the amino acids taurine, L-glutamine and L-arginine. Regul Toxicol Pharmacol 2008. Read 2026-10-22.
- NCCIH: Using dietary supplements wisely. Read 2026-10-22.
Education, not medical advice. This page is for general information. It does not diagnose or treat any condition and is not a substitute for care from a qualified health professional. Natural does not automatically mean safe. Ask a clinician or pharmacist before changing your care, especially if you take medication, are pregnant or breastfeeding, or have a health condition.