Arginine, Citrulline, Nitric Oxide and Blood Pressure: What Trials Show
What clinical trials and reviews found for arginine and citrulline on blood pressure and exercise, plus the heart-attack, pregnancy and medicine cautions to know first.
Content last updated . This page has not been medically reviewed.
Quick answer
Several small trials and meta-analyses report that arginine or citrulline lowers blood pressure by a few points on average, but the trials are short, small and varied, and the findings do not show that either product prevents heart attacks or strokes. Citrulline malate has a small, uncertain effect on exercise performance. Neither replaces treatment prescribed by a clinician.
What arginine and citrulline are
Arginine is a protein-building amino acid. Sources classify it differently: one 2026 review calls it semi-essential or conditionally essential [2], while a 2023 review lists it among the nonessential amino acids. [3] Citrulline is not used to build proteins; the same review calls it a nonproteinogenic amino acid. [3] The body can turn citrulline into arginine, partly in the kidneys. [4] Arginine is a substrate (a starting material) for the enzyme that makes nitric oxide, a molecule that relaxes blood vessels. [1] That is the reason for the interest in blood pressure. For the wider classification, see What Are Amino Acids?.How to read the evidence labels
"Promising but limited" means controlled trials show an effect but are small or short. "Mixed" means results differ. "Evidence of harm" means a trial raised a safety signal. A blood pressure reading is not the same as fewer heart attacks.What research found
| Question | What the source found | Strength of evidence |
|---|---|---|
| Oral arginine and blood pressure | A 2011 meta-analysis of 11 placebo-controlled trials (387 people, study amounts 4 to 24 g a day) found systolic pressure 5.39 mm Hg lower than placebo. [5] A 2026 meta-analysis of 5 trials (202 people) using 24-hour monitoring found 24-hour systolic pressure 4.23 mm Hg lower; the authors note the number of studies was limited. [6] | Promising but limited |
| Citrulline (including watermelon) and blood pressure in middle-aged and older adults | A 2025 meta-analysis of 15 trials (24 datasets, 415 people) found systolic pressure 4.02 mm Hg lower. [7] It pooled citrulline supplements with watermelon intake. | Promising but limited |
| Arginine after a heart attack | Higher deaths in the arginine group in one trial. [1] | Evidence of harm (single trial) |
| Citrulline malate and exercise | A 2026 meta-analysis of 30 trials found a small improvement overall, with wide uncertainty and GRADE certainty low to very low. [8] An earlier analysis of 8 studies found about 3 more repetitions to failure after 6 to 8 g taken 40 to 60 minutes before exercise (a study amount). [9] | Mixed; small effect |
| Arginine in pregnancy (pre-eclampsia) | A 2025 review of 20 trials found a lower pre-eclampsia risk (RR 0.52) in prevention trials, but low-certainty evidence; only one small citrulline study was found, with no effect. [10] | Promising but limited |
Related pages
See L-Arginine and L-Citrulline and the head-to-head L-Arginine vs L-Citrulline. A broader look at amino acids and the heart is at Amino Acids, Heart Disease and Blood Pressure.Frequently asked questions
Does arginine lower blood pressure?
In short trials pooled in meta-analyses, systolic pressure was about 4 to 5 mm Hg lower than with placebo. [5] [6] The number of studies is limited, and this does not show fewer heart attacks.
Is citrulline better than arginine?
We did not find a trial in the sources we read that compared them head to head for blood pressure. One review describes citrulline as efficiently moving into gut cells and being converted to arginine by the kidneys. [4] See the comparison page for details.
Does citrulline malate improve workouts?
A 2026 meta-analysis found a small improvement with low to very low certainty. [8]
Can I take arginine with blood pressure medicine?
Ask your pharmacist or prescriber. The trials we read mostly do not answer this question, and arginine acts on the nitric oxide pathway. [5] [1] Never stop a prescribed medicine on your own.
Is arginine safe in pregnancy?
Reviewed trials were supervised and the evidence is low certainty. [10] Ask your obstetric clinician before using it.
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.
Safety first
Do not use arginine as a supplement after a heart attack unless the doctor treating you says so. In one randomized trial of 153 people after a first heart attack, 6 of the people given arginine (goal of 3 g three times a day, for 6 months) died, compared with none on placebo, and the trial's authors concluded that arginine should not be recommended after an acute heart attack. [1] That is one trial, but it is the reason this page asks you to involve a clinician before using these products if you have heart disease, low blood pressure or take blood pressure medicines. If someone has chest pain, fainting or severe breathlessness, call 911 (in the US).
Limits and uncertainty
The 2011 analysis checked trials where people were not using blood pressure medicines and found similar results [5]; we did not find a source that tested arginine in people who take such medicines. A review of these trials also notes that more research with larger groups is needed. [11] Diarrhea was seen in two of the six arginine trials that reported side effects. [11] For citrulline malate, a 2026 review concludes reliable dosing, timing and target groups have not been established. [8]
Medicines, pregnancy, children and surgery
- Blood pressure medicines and nitrates (angina medicines): we did not find a source we read that tested arginine or citrulline together with these medicines. Because arginine feeds the nitric oxide pathway [1], ask a pharmacist before combining them. See Medication Interactions.
- Pregnancy and breastfeeding: the trials above were supervised study settings, not advice to self-treat. Talk to your obstetric clinician first. See pregnancy and breastfeeding safety.
- Children, kidney or liver conditions, and before surgery: Proper evidence not found in the sources we read (we searched PubMed for arginine and citrulline reviews and trials). Ask a clinician or pharmacist; see Supplements Before Surgery.
- Official limits: a 2023 review states that national health agencies have not set tolerable upper intake levels for amino acids. [3] We therefore quote none.
- Pre-workout blends: citrulline products may contain other ingredients; see Pre-Workout and Energy Drink Amino Acid Blends and Quality Testing and Certifications.
References
- Schulman SP, et al. L-arginine therapy in acute myocardial infarction: the VINTAGE MI randomized clinical trial. JAMA 2006. PubMed record PMID 16391217. Read 2026-10-23.
- Al-Qusous MN, et al. The amino acid arginine: a comprehensive review. Clin Nutr ESPEN 2026. PubMed record PMID 41887327. Read 2026-10-23.
- Elango R. Tolerable Upper Intake Level for Individual Amino Acids in Humans: a narrative review of recent clinical studies. Adv Nutr 2023. PubMed record PMID 37062432. Read 2026-10-23.
- Papadia C, et al. Citrulline in health and disease. Review on human studies. Clin Nutr 2018. PubMed record PMID 29107336. Read 2026-10-23.
- 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. PubMed record PMID 22137067. Read 2026-10-23.
- 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. PubMed record PMID 42520885. Read 2026-10-23.
- Luo P, et al. Does l-citrulline supplementation and watermelon intake reduce blood pressure in middle-aged and older adults? A systematic review and meta-analysis of randomized controlled trials. Clin Nutr ESPEN 2025. PubMed record PMID 40789388. Read 2026-10-23.
- Wang X, et al. Effects of Citrulline Malate Supplementation on Exercise Performance: a systematic review and three-level meta-analysis. Nutrients 2026. PubMed record PMID 42356270. Read 2026-10-23.
- Vårvik FT, Bjørnsen T, Gonzalez AM. Acute Effect of Citrulline Malate on Repetition Performance During Strength Training: a systematic review and meta-analysis. Int J Sport Nutr Exerc Metab 2021. PubMed record PMID 34010809. Read 2026-10-23.
- Makama M, et al. L-Arginine and L-Citrulline for Prevention and Treatment of Pre-Eclampsia: a systematic review and meta-analysis. BJOG 2025. PubMed record PMID 39800868. Read 2026-10-23.
- The Effects of Oral l-Arginine and l-Citrulline Supplementation on Blood Pressure (review article, Nutrients 2019, PubMed Central). Read 2026-10-23.
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.