L-Arginine and L-Citrulline
L-arginine and L-citrulline explained: how each is classified, what trials show for blood pressure and exercise, the heart attack trial warning, and the limits of the evidence.
Content last updated . This page has not been medically reviewed.
What is Arginine and citrulline good for?
What the body uses it for, and how strong the evidence is. A normal job in the body is not proof that extra supplements add benefit; each card says which.
Nitric oxide production (arginine)
Established roleArginine is the raw material the body's enzyme (nitric oxide synthase) uses to make nitric oxide, a molecule that helps blood vessels relax.
Supplements: This is normal biology. It does not by itself show that extra arginine from supplements widens vessels or helps health; trials have been mixed.
Blood pressure (arginine)
Preliminary or mixedIn a meta-analysis of 22 placebo-controlled trials, arginine lowered blood pressure by a few points on average, but not at the highest amounts, in longer trials, or in people with obesity.
Supplements: Promising but limited: a small average drop in trials is not a promise for one person, and high blood pressure needs a clinician.
Blood pressure (citrulline)
Preliminary or mixedA 2025 meta-analysis of 15 trials found lower blood pressure with citrulline and watermelon combined in middle-aged and older adults.
Supplements: Watermelon and citrulline are different products, so this does not prove citrulline alone works.
Building block for proteins (arginine)
Established roleArginine is an amino acid, one of the building blocks the body strings together into proteins.
Supplements: The body usually makes enough; supplements are not shown to add benefit in healthy people.
Conditionally essential in illness and stress (arginine)
Preliminary or mixedArginine is not essential for most people, but it can become needed during illness or stress. Low arginine availability has been described in sickle cell disease, trauma and pulmonary hypertension.
Supplements: Applies to specific illnesses under medical care, not to healthy people buying supplements.
Endurance exercise (citrulline)
Not enough evidenceTwo meta-analyses found no significant endurance benefit from citrulline in healthy young adults.
Supplements: No benefit shown in healthy adults in the reviews read.
Muscle strength (citrulline malate)
Not enough evidenceA meta-analysis of 4 studies in resistance-trained adults found no improvement in muscle strength.
Supplements: No benefit shown in resistance-trained adults in the review read.
Muscle mass and strength (arginine and citrulline)
Preliminary or mixedA review of muscle supplements placed both arginine and citrulline in the mixed or unclear group.
Supplements: Mixed or unclear; some adverse events were reported with large intakes of arginine.
Connected topics
Open a group to see how each topic connects and how strong the evidence is.
Health goals (2)
- Blood Pressure SupportPreliminary or mixed
Arginine lowered blood pressure by a few points on average in a meta-analysis of 22 trials, and citrulline with watermelon did so in another. Evidence is promising but limited and does not replace medical care.
- Heart HealthDocumented risk
In a trial after a first heart attack, more people died in the arginine group, and the authors advised against its use there. People with heart disease should ask their cardiologist.
Body systems (2)
- Cardiovascular SystemPreliminary or mixed
Arginine feeds the body's nitric oxide pathway, and trials show small average blood pressure falls. A trial after a heart attack reported more deaths with arginine.
- Heart & CirculationPreliminary or mixed
Arginine and citrulline have been studied for blood pressure with small average falls; arginine is not advised after a heart attack.
Body parts (2)
- Blood VesselsEstablished role
Arginine is the raw material for nitric oxide, which helps blood vessels relax. Whether extra supplements help is unproven.
- HeartDocumented risk
A trial in 153 people after a first heart attack found no improvement in heart function and more deaths with arginine.
Functional actions (2)
- Cardiovascular SupportPreliminary or mixed
Blood pressure fell slightly on average in trials, but this is a blood pressure marker, not fewer heart attacks, and arginine is not advised after a heart attack.
- Circulation SupportPreliminary or mixed
Arginine is a substrate for nitric oxide, which relaxes vessels; trial results on vascular stiffness were mixed.
Conditions & symptoms (3)
- Myocardial InfarctionDocumented risk
In a 6-month trial after a first heart attack, 6 people (8.6%) in the arginine group died versus none on placebo; the authors concluded arginine should not be recommended after a heart attack.
- Essential HypertensionPreliminary or mixed
Meta-analyses show small average blood pressure falls with arginine and with citrulline/watermelon. Evidence is promising but limited; high blood pressure needs clinical care, and arginine may add to blood pressure medicines.
- Pulmonary HypertensionPreliminary or mixed
A review notes low arginine availability is involved in pulmonary hypertension. This describes an association in illness, not proof that supplements treat it.
Documented risks and interactions (2)
- Safety after a heart attack (arginine). In a trial of 153 people after a first heart attack, more people on arginine died than on placebo, and the authors advised against its use in that setting.
- Kidney effects (arginine). A review found arginine may have both beneficial and detrimental effects on kidney function; adverse effects were unlikely at routine amounts in athletes.
Urgent safety point first
In a 6-month trial of 153 people after a first heart attack, L-arginine added to standard care did not improve vascular stiffness or heart function, and 6 people (8.6%) in the arginine group died versus none on placebo. The safety committee closed enrollment, and the authors concluded L-arginine should not be recommended after a heart attack. [1] Anyone with heart disease should talk to their cardiologist before using arginine.Quick answer
L-arginine is an amino acid that the body usually makes, so it is not essential. MedlinePlus lists it as nonessential and also as conditionally essential, meaning it may be needed in illness and stress. [2] A review notes that low arginine availability is involved in conditions including sickle cell disease, trauma and pulmonary hypertension. [3] Arginine is a substrate for nitric oxide synthase, the enzyme that makes nitric oxide, and earlier studies suggested it might reduce vascular stiffness. [1] That is the reasoning behind its marketing for blood pressure and exercise.L-citrulline is a different compound. A 2023 review classes it as a nonproteinogenic amino acid, meaning it is not a building block of body proteins. [4] Citrulline is sold alone or as citrulline malate. Neither is one of the nine essential amino acids; see essential amino acids.
Evidence by use
Labels: promising but limited, mixed, and no benefit shown in healthy adults. Biomarker or blood pressure changes in trials are not the same as fewer heart attacks.| Question | What the sources found | Label |
|---|---|---|
| Arginine and blood pressure | A 2022 meta-analysis of 22 placebo-controlled trials found average falls of 6.4 mmHg (systolic) and 2.6 mmHg (diastolic); no significant change was seen at amounts above 9 g a day, in trials longer than 24 days, or in people with obesity. [5] A 2026 analysis of 5 trials (202 people) using 24-hour monitoring also found lower pressure but said the number of studies was limited. [6] | Promising but limited |
| Citrulline or watermelon and blood pressure | A 2025 meta-analysis of 15 trials (415 middle-aged and older adults) found lower systolic and diastolic pressure with citrulline and watermelon combined. [7] Watermelon and citrulline are different products, so this does not prove citrulline alone works. | Promising but limited |
| Citrulline and endurance | Two meta-analyses (9 studies in 158 young healthy adults; 10 studies) found no significant benefit. [8][9] | No benefit shown in healthy adults |
| Citrulline malate and strength | A meta-analysis of 4 studies in resistance-trained adults found no improvement in muscle strength. [10] | No benefit shown in healthy adults |
| Arginine and citrulline for muscle | A review of muscle supplements put both in the "mixed or unclear" group. [11] | Mixed |
| Other marketed uses (for example sexual function) | Not assessed on this page: none of the reviews we read covered them, so no claim is made. | Proper evidence not found in the sources we read |
High blood pressure needs proper assessment and treatment by a clinician. A drop of a few points in a trial average is not a promise for one person. For the wider picture see amino acids, heart disease and blood pressure.
Amounts and official limits
Amounts in studies are study amounts, not advice. A risk assessment found strong evidence of no adverse effects for arginine at supplemental intakes up to 20 g a day in healthy adults. [12] A 2023 review reported a no-observed-adverse-effect level of 30 g a day for arginine and 24 g a day for citrulline in healthy adults, from studies run under an amino acid nonprofit's initiative; it also noted that no national health agency has set upper limits for individual amino acids. [4] These figures do not apply to people with heart or kidney disease. No official recommended intake for arginine or citrulline was found in the sources we read.Frequently asked questions
Is arginine an essential amino acid?
No. It is usually made by the body and is conditionally essential in some illnesses. [2]
Is citrulline an amino acid?
It is a nonproteinogenic amino acid, not a building block of proteins. [4]
Does arginine lower blood pressure?
A meta-analysis of 22 trials found an average fall of 6.4 mmHg systolic, but not at amounts above 9 g a day or in trials longer than 24 days. [5]
Does citrulline improve exercise performance?
Meta-analyses found no significant benefit for endurance or for strength in healthy adults. [8][9][10]
Who should avoid arginine?
People who have had a heart attack: a trial reported more deaths in the arginine group, and the authors advised against its use. [1] Others with heart, kidney or blood pressure concerns should ask a clinician first.
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.
Other cautions
- Blood pressure medicines. Arginine lowered blood pressure in trials, so tell your prescriber or pharmacist before combining it with blood pressure medicines. [5] See how interactions work.
- Kidneys. A review found arginine may have both beneficial and detrimental effects on kidney function, though adverse effects were unlikely at routine amounts in athletes. [13]
- Large intakes. A review of muscle supplements reported some adverse events with large intakes of arginine. [11]
- Pregnancy, breastfeeding, children, older adults, liver disease and surgery. Not described in the sources we read. Ask a clinician. See pregnancy and breastfeeding and supplements before surgery.
- Pre-workout blends. These can add caffeine or other stimulants; check labels with reading supplement labels.
Related: beets and beet juice, protein for muscle, training and recovery and glutamine.
References
- Schulman SP et al. L-arginine therapy in acute myocardial infarction: the VINTAGE MI randomized clinical trial. JAMA 2006. Read 2026-10-22.
- MedlinePlus. Amino acids. National Library of Medicine, US (reviewed 1/21/2025). 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.
- Elango R. Tolerable upper intake level for individual amino acids in humans: a narrative review of recent clinical studies. Adv Nutr 2023. Read 2026-10-22.
- Shiraseb F et al. Effect of L-arginine supplementation on blood pressure in adults: a systematic review and dose-response meta-analysis. Adv Nutr 2022. Read 2026-10-22.
- Shi Y et al. Reassessment of the effect of oral L-arginine on blood pressure: a systematic review and meta-analysis based on ambulatory blood pressure monitoring. Nitric Oxide 2026. Read 2026-10-22.
- Luo P et al. Does L-citrulline supplementation and watermelon intake reduce blood pressure in middle-aged and older adults?. Clin Nutr ESPEN 2025. Read 2026-10-22.
- Harnden CS et al. Effects of citrulline on endurance performance in young healthy adults: a systematic review and meta-analysis. J Int Soc Sports Nutr 2023. Read 2026-10-22.
- Viribay A et al. Effects of citrulline supplementation on different aerobic exercise performance outcomes: a systematic review and meta-analysis. Nutrients 2022. Read 2026-10-22.
- Aguiar AF, Casonatto J. Effects of citrulline malate supplementation on muscle strength in resistance-trained adults: a systematic review and meta-analysis. J Diet Suppl 2022. Read 2026-10-22.
- Valenzuela PL et al. Supplements with purported effects on muscle mass and strength. Eur J Nutr 2019. 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.
- Davani-Davari D et al. The renal safety of L-carnitine, L-arginine, and glutamine in athletes and bodybuilders. J Ren Nutr 2019. Read 2026-10-22.