L-arginine and L-citrulline for ED: what the trials found

Status: Dietary supplement: not FDA-approved to treat any disease. Source: FDA, Questions and Answers on Dietary Supplements, checked 2026-10-17.

In short: L-arginine and L-citrulline are two amino acids that show up on almost every “natural ED” shelf. The idea behind them is sound biology: the body uses arginine to make nitric oxide, a molecule that relaxes blood vessels. The trials are a different story. They are small, they mostly enrolled men with mild to moderate ED, and they do not show these supplements working as well as prescription ED medicines. This page sets out what the studies found, the blood pressure cautions, and where a clinician fits in.

Evidence: mixed or small trials.

What are L-arginine and L-citrulline?

They are amino acids, building blocks the body uses to make protein. Mayo Clinic notes that the body usually makes all the L-arginine it needs, and that it is also found in protein-rich foods such as fish, red meat, poultry, soy, whole grains, beans and dairy (Mayo Clinic, L-arginine). The NIH Office of Dietary Supplements (ODS) explains that the body also makes arginine from citrulline, mainly in the kidneys (ODS, Dietary Supplements for Exercise and Athletic Performance). So citrulline is, in effect, a route to more arginine. Watermelon is a natural source of citrulline, though we found no trial of eating it for ED, as our pages on diet and ED and viral ED tricks explain.

How are they supposed to work?

They are meant to feed the nitric oxide pathway that erections rely on. ODS says some arginine is converted to nitric oxide, “a potent vasodilator,” which means it widens blood vessels (ODS fact sheet). In the penis, nitric oxide helps the smooth muscle relax so blood can flow in, the same pathway that prescription ED pills act on further downstream, as our guide to how ED medications work describes. Citrulline is used because, as the authors of one trial put it, swallowed arginine is heavily broken down before it reaches the bloodstream, while citrulline avoids that and is then converted to arginine (Cormio and colleagues, Urology, 2011).

What did trials find for L-arginine?

The trials point to a modest benefit in men with mild to moderate ED, from a small and uneven evidence base. The table sums up the three main pieces of evidence we read.

Two cautions apply across this evidence. First, the main scores come from questionnaires based on men’s own reports, which the 2023 authors note are subjective. Second, several trials tested arginine mixed with other ingredients, so the result of a combination product does not tell you what arginine alone does. Small trials like these are a starting point rather than a settled answer.

What did trials find for L-citrulline?

The evidence for citrulline is thinner still: one small pilot study. In it, 24 men with mild ED took a placebo for one month and L-citrulline for the next month, in a single-blind design (Cormio and colleagues, Urology, 2011). Erection firmness improved from mild ED to the normal range in 12 of the 24 men (50%) on citrulline, compared with 2 of 24 (8.3%) on placebo, and no side effects were reported. The authors themselves called citrulline “less effective” than prescription ED medicines, at least in the short term, and said its role “deserves further research.”

How do they compare with ED medicines?

No head-to-head trial in the studies we read showed either supplement matching a prescription ED medicine. The citrulline authors said it was less effective than PDE5 inhibitors, the drug class that includes sildenafil and tadalafil (Cormio and colleagues), and the 2022 arginine trial framed arginine as a possible alternative for men with mild to moderate ED from blood-flow problems who have side effects from those medicines or cannot take them long term (Menafra and colleagues). The National Center for Complementary and Integrative Health (NCCIH) puts it more bluntly: “No complementary health approaches have been shown to be safe and effective” for treating ED (NCCIH, What the Science Says). For a wider look at the options, see natural remedies for ED vs medication.

Are there safety concerns with blood pressure medicines?

Yes. Because L-arginine might lower blood pressure, Mayo Clinic says combining it with a blood pressure medicine, herb or supplement “might increase the risk of blood pressure becoming too low,” and advises anyone on a blood pressure drug to talk with a doctor before using it (Mayo Clinic, L-arginine). Mayo lists the same low blood pressure concern with nitrate chest pain medicines and with sildenafil, the active ingredient in Viagra. It also flags these other possible interactions and cautions:

• Blood thinners and anti-platelet medicines: a possible higher risk of bleeding.
• Diabetes medicines: L-arginine might lower blood sugar in people with diabetes.
• Potassium-sparing water pills such as spironolactone: a risk of high potassium levels.
• A recent heart attack: Mayo says L-arginine is not recommended. In one randomized trial in heart attack survivors, 6 of the participants taking L-arginine died during the six-month study versus none on placebo, and the authors concluded it “should not be recommended” after a heart attack (Schulman and colleagues, JAMA, 2006).
• Asthma or allergies: L-arginine can make them worse.

Common side effects Mayo lists for oral L-arginine include nausea, stomach pain, diarrhea, bloating and headache. In the ED trials, side effects were uncommon and none were severe: 8.3% on arginine versus 2.3% on placebo in the 2019 meta-analysis (Rhim and colleagues). ODS adds that the safety of taking high-dose arginine for more than three months is not known (ODS fact sheet). If you take medicine for blood pressure, our page on blood pressure medications and ED covers how those drugs themselves fit into the picture.

Are they approved to treat ED?

No. Both are sold as dietary supplements, and FDA “does not have the authority to approve dietary supplements before they are marketed” (FDA, Questions and Answers on Dietary Supplements). FDA also says a product sold as a supplement that claims to treat, prevent or cure a disease meets the definition of a drug, which is why a supplement label that makes a claim about how the product affects the body must carry a disclaimer that it is not intended to “diagnose, treat, cure, or prevent any disease.” A related risk: FDA warns that many products sold for sexual enhancement or ED “are likely to be contaminated with dangerous hidden ingredients” (FDA, Sexual Enhancement and Energy Product Notifications), and NCCIH notes that some of those hidden drug ingredients may interact with nitrates, leading to a dangerous drop in blood pressure. FDA adds that these products are sometimes falsely advertised as dietary supplements or all-natural treatments; see our page on hidden drugs in “natural” ED pills.

When should I talk to a clinician?

Before you start, ideally. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) advises talking with a health care professional before using dietary supplements or alternative medicines for ED, for safety reasons (NIDDK, Treatment for ED). That matters even more if you take blood pressure, heart, blood-thinning or diabetes medicines. NIDDK also notes that health care professionals treat the underlying cause of ED when possible, and that diabetes, high blood pressure and heart and blood vessel disease can lead to ED. A supplement does not check for any of these; our guide on when to see a doctor about ED covers the signs that call for an appointment.

The bottom line

L-arginine has a modest, small-trial evidence base in men with mild to moderate ED, and L-citrulline rests on a single pilot study. Neither is FDA-approved for ED, neither has matched a prescription medicine in the trials we read, and L-arginine carries real blood pressure and heart cautions. If you are curious about them, bring the question to a clinician, who can weigh them against your medicines and against treatments with stronger evidence.

Sources

• Rhim HC and colleagues. The Potential Role of Arginine Supplements on Erectile Dysfunction: A Systemic Review and Meta-Analysis. J Sex Med, 2019. 10 RCTs, 540 men with mild to moderate ED; improvement versus placebo or no treatment; side effects 8.3% versus 2.3%, none severe: pubmed.ncbi.nlm.nih.gov/30770070
• Menafra D and colleagues. Long-term high-dose L-arginine supplementation in patients with vasculogenic erectile dysfunction: a multicentre, double-blind, randomized, placebo-controlled clinical trial. J Endocrinol Invest, 2022. 98 men with mild to moderate vasculogenic ED (51 on arginine, 47 on placebo); IIEF-6 gains versus placebo; 74% of the arginine group who finished improved ED category and 24% reached scores consistent with no ED: pmc.ncbi.nlm.nih.gov/articles/PMC8995264
• Tian Y and colleagues. Efficacy of L-arginine and Pycnogenol in the treatment of male erectile dysfunction: a systematic review and meta-analysis. Frontiers in Endocrinology, 2023. 3 studies, 184 men; few studies is the main limitation: pmc.ncbi.nlm.nih.gov/articles/PMC10614297
• Cormio L and colleagues. Oral L-citrulline supplementation improves erection hardness in men with mild erectile dysfunction. Urology, 2011. Single-blind pilot, 24 men; 50% versus 8.3% improved: pubmed.ncbi.nlm.nih.gov/21195829
• NIH Office of Dietary Supplements. Dietary Supplements for Exercise and Athletic Performance, arginine and citrulline sections. Arginine made from citrulline, conversion to nitric oxide, long-term safety unknown: ods.od.nih.gov
• NCCIH. Dietary Supplements Marketed for Weight Loss, Bodybuilding, and Sexual Enhancement: What the Science Says. No complementary approach shown safe and effective for ED; adulteration and nitrate risk: nccih.nih.gov
• Mayo Clinic. L-arginine. Food sources, side effects, interactions with blood pressure drugs, nitrates and sildenafil, and the recent heart attack caution: mayoclinic.org
• Schulman SP and colleagues. L-arginine therapy in acute myocardial infarction: the VINTAGE MI randomized clinical trial. JAMA, 2006. 6 deaths on L-arginine versus none on placebo: pubmed.ncbi.nlm.nih.gov/16391217
• FDA. Questions and Answers on Dietary Supplements. No premarket approval of supplements; disease claims make a product a drug: fda.gov
• FDA. Sexual Enhancement and Energy Product Notifications. Hidden ingredients in products sold for ED; some falsely advertised as supplements or all-natural treatments: fda.gov
• NIDDK. Treatment for Erectile Dysfunction. Talk with a health care professional before using supplements; diabetes, high blood pressure and heart and blood vessel disease can lead to ED: niddk.nih.gov