Vitamins & Supplements · Amino acid
Arginine and citrulline
L-arginine and L-citrulline · also called Arginina, citrulina, citrulline malate
Arginine and citrulline are amino acids the body uses to make nitric oxide, which helps blood vessels relax. Arginine comes from protein foods such as seeds, nuts, poultry and meat. Trials show small average drops in blood pressure, but the evidence is low-certainty, and citrulline has not been shown to help exercise. One trial after a heart attack found more deaths on arginine, so people with heart disease should ask a doctor first.
General information, not medical advice. Last substantive update · Not medically reviewed. A named clinician has not signed off on this page. How this page is made
About Arginine and citrulline
Arginine is an amino acid in protein foods that the body also makes; citrulline is a related amino acid the body can turn into arginine. Both are sold as supplements to help blood flow, exercise and men's vitality. Evidence shows small blood pressure drops, little for exercise, and a warning after a heart attack.
What arginine and citrulline are
Arginine is an amino acid. MedlinePlus (page reviewed January 2025) lists it as a nonessential amino acid and also as a conditionally essential one: usually not essential, except in illness and stress. The body uses arginine to make nitric oxide, a molecule that helps blood vessels relax.
Citrulline is a related amino acid that is not a building block of body proteins and is a precursor of arginine. It is sold alone or as citrulline malate. Product forms are described on this page only as they appear in the studies.
Where arginine comes from in food
Protein foods carry arginine. USDA data (per portion): pumpkin seeds, about 1.5 g in an ounce; walnuts, about 2.7 g in a cup chopped; roasted chicken breast, about 1.6 g in half a breast; farmed salmon, about 1.1 g in 3 oz cooked; broiled 85% lean beef patty, about 1.0 g in 3 oz; cooked lentils, about 1.4 g a cup; cooked chickpeas, about 1.4 g a cup; a hard-boiled egg, about 0.4 g. A cup of diced watermelon has only about 0.09 g.
Watermelon is often named as a citrulline food, but USDA SR Legacy tables have no citrulline value, so none is given here.
When the body may fall short
A 2017 review says arginine can become low in stress and illness, including sickle cell disease, malaria, acute asthma, cystic fibrosis, pulmonary hypertension and trauma, mostly because arginase enzymes break it down. This describes what happens in disease. It does not show that arginine pills treat these conditions.
Two rare inherited conditions, arginase deficiency and citrullinemia, make arginine or ammonia build up in the blood. They need specialist care.
What the research shows
The best-supported finding is a small average drop in blood pressure with arginine (low certainty); citrulline with watermelon showed something similar in older adults. Results for erectile function and pre-eclampsia are promising but low-certainty. Citrulline did not improve endurance or strength in meta-analyses, and arginine did not change blood sugar markers.
After a heart attack, one trial found more deaths with arginine, and its authors advised against it. Most trials are small, pool different products and amounts, and were read as abstracts only.
Food versus pills
Almost all of the trial results above are for supplements. Foods supply arginine together with other amino acids in small amounts, and no trial compared food with pills. The blood pressure review for citrulline pooled pills and watermelon, so it does not separate them. If you wonder about your own needs, ask a doctor, pharmacist or dietitian.
At a glance
Traditional uses history, not proof
- Amino acids from protein foods
- Sold as powders and capsules for circulation, exercise and men's vitality
Studied for research
- Body role and food sources, high certainty
- Blood pressure (arginine), low certainty
- Blood pressure (citrulline with watermelon), low certainty
- Erectile function, pre-eclampsia, low certainty
- Muscle mass and strength, mixed evidence
- Citrulline for endurance and strength, low certainty of benefit
- Heart attack recovery, evidence against
Main compounds
- L-arginine
- L-citrulline
- Citrulline malate
- Arginine hydrochloride (the form given in a vein in a 1978 case report)
Common forms
- Food sources (seeds, nuts, poultry, meat, fish, legumes)
- Powders, capsules and tablets
- Pre-workout blends with citrulline malate
Research links: 2022 meta-analysis: arginine and blood pressure (22 trials) · 2026 meta-analysis: arginine and 24-hour blood pressure (5 trials) · 2025 meta-analysis: citrulline and watermelon and blood pressure · 2006 VINTAGE MI trial: arginine after a heart attack · 2025 meta-analysis: arginine and citrulline in pre-eclampsia · Research Library · Genes & Biomarkers Library
What it is and its history
- Accepted scientific name
- Arginine and citrulline (L-arginine and L-citrulline, two amino acids)
- Common names
- L-arginine (English); Arginine (English); L-citrulline (English); Citrulline (English); Citrulline malate (English); Arginina (Spanish); Citrulina (Spanish)
- Family or group
- Amino acids. MedlinePlus lists arginine as nonessential and as conditionally essential (usually not essential, except in illness and stress). Citrulline is described in a 2023 review as a nonproteinogenic amino acid and in a 2025 review as a precursor of arginine.
- Look-alikes and adulterants
- Name: Ornithine; Note: Another amino acid reviewed with arginine and citrulline in a 2023 tolerance review; a 2019 review placed it in the group with no evidence for muscle.; Name: Glutamine; Note: Another conditionally essential amino acid; it has its own page.; Name: Carnitine; Note: An amino acid derivative reviewed with arginine in a kidney-safety review; it has its own page.
- Sustainability and conservation
- Not assessed.
What is inside, and how it may work
What it contains and how those compounds act in cells and animals. Laboratory and animal mechanisms are not proven effects in people.
Main compounds
| Compound | Family | Where it is concentrated | Activity studied | Level of evidence |
|---|---|---|---|---|
| L-arginine | amino acid | Not read from a source. | Substrate for nitric oxide synthase (VINTAGE MI trial abstract); tested for blood pressure, erectile function, blood sugar, pre-eclampsia and after a heart attack. 10 12 16 6 8 | Human data |
| L-citrulline | amino acid | Not read from a source. | A precursor of arginine (2025 review); tested for blood pressure (pooled with watermelon) and endurance. 8 7 5 | Human data |
| Citrulline malate | amino acid salt | Not read from a source. | Citrulline combined with malate; tested for muscle strength in resistance-trained adults. 1 | Human data |
| Arginine monohydrochloride | amino acid salt | Not read from a source. | The form given into a vein in the 1978 potassium case report; not a supplement form. 2 | Human data |
Mechanisms, receptors and pathways
| Target or pathway | Gene or receptor | What was found | Level |
|---|---|---|---|
| Nitric oxide production | Nitric oxide synthase (enzyme) | The VINTAGE MI trial abstract states arginine is a substrate for nitric oxide synthase. Nitric oxide helps blood vessels relax. This is the proposed route for the blood pressure and erectile function research; the trials measured outcomes, not the pathway. 10 | Human data |
| Arginine breakdown by arginase | Arginase enzymes | A 2017 review says breakdown of arginine by arginase enzymes is the most common cause of an acquired arginine shortage in illness, often contributing to blood vessel and T-cell problems. 9 | Human data |
| Citrulline as a precursor of arginine | Not given in the abstract | A 2025 review calls citrulline a precursor of arginine, which is the reason it is studied for blood pressure and exercise. 8 7 | Human data |
| Potassium shift out of cells | Not given in the abstract | A 1978 case report says arginine shifts potassium from cells into the blood, an effect related to its blood level. 2 | Human data |
Absorption, metabolism and elimination
- Absorption
- Not found in the sources read.
- Distribution
- Not found in the sources read.
- Metabolism
- A 2017 review says arginine is broken down by arginase enzymes, and citrulline is a precursor of arginine (2025 review). Details were not read.
- Elimination
- Not found in the sources read.
- Bioavailability
- Not compared across forms (arginine, citrulline, citrulline malate) in the sources read.
Isolated compounds versus whole extracts
Food and pills are not the same. Foods bring arginine together with other amino acids, fat and fibre, and in ordinary portions the amounts are small (see the food list). Almost all of the trial results on this page are for supplements, often at much higher amounts than a meal. No trial comparing arginine or citrulline from food with pills was read. Watermelon was pooled with citrulline pills in the blood pressure review, so that result does not separate them.
Nutritional composition
Arginine content of foods is from USDA FoodData Central SR Legacy (April 2018 release), read 2026-10-26 from a saved local copy; values are per 100 g and per household portion. SR Legacy has no citrulline value, so no citrulline amount is given for any food.
2 high certainty1 mixed findings7 low certainty1 evidence against
What was looked at
The 11 benefits and uses checked for Arginine and citrulline, each with how strong the evidence is. Tap one to open it.
- What they do in the bodyHigh certainty
- Food sources of arginine and citrullineHigh certainty
- Blood pressure (arginine)Low certainty
- Blood pressure (citrulline and watermelon)Low certainty
- Endurance exercise (citrulline)Low certainty
- Muscle strength (citrulline malate)Low certainty
- Muscle mass and strength (arginine and citrulline)Mixed findings
- Erectile dysfunction (arginine)Low certainty
- Blood sugar control (arginine)Low certainty
- Pre-eclampsia in pregnancy (arginine)Low certainty
- Recovery after a heart attack (arginine)Evidence against
Lab markers tracked in the studies
Systolic blood pressure (top number)Diastolic blood pressure (bottom number)24-hour (ambulatory) blood pressureFasting glucose, HbA1c and insulin resistanceTime to exhaustion and time to complete an effortPre-eclampsia
What is Arginine and citrulline good for?
The main studied uses and how strong the human evidence is for each. Most results are for supplements in adults, and several are small studies pooled together.
Benefits, one by one
Each card is a research question, not a promise. Tap a goal to filter. Open a card to see the studies, doses and limits.
What they do in the body
High certaintyArginine is an amino acid, a building block of protein. MedlinePlus lists it as a nonessential amino acid and also as a conditionally essential one: the body usually makes enough, but may need more in illness and stress. Citrulline is a related amino acid that is not a building block of body proteins and is a precursor of arginine. Low arginine availability has been described in several illnesses.
4 studiesArginine and citrulline as nutrients from food and supplements; forms…
Studies, doses and limits
What the trials found
MedlinePlus (review date 2025-01-21) says arginine is usually not essential except in times of illness and stress. A 2017 review says low arginine availability plays a role in sickle cell disease, thalassaemia, malaria, acute asthma, cystic fibrosis, pulmonary hypertension, cardiovascular disease, some cancers and trauma, and that breakdown by arginase enzymes is the most common cause. That is an association in illness, not a trial showing supplements treat these. No trial in healthy, well-fed adults showing a benefit from extra arginine or citrulline for general health was read.
Results
Arginine is made by the body and eaten in protein foods. A shortage can happen in illness. Extra pills have not been shown to help healthy people in general.
Effect sizes as reported
No effect sizes apply: these are body roles, not trial results.
Why this rating
High that arginine is a conditionally essential amino acid (MedlinePlus). The illness associations come from a narrative review, so they are not graded as treatment evidence.
Form and dose studied
Arginine and citrulline as nutrients from food and supplements; forms are described in the Overview.
Who was studied
General population; people who are ill or under stress in the review.
Limits
A narrative review and an encyclopedia page. Neither shows that supplements prevent or treat the illnesses listed.
Why researchers looked
People ask whether they need extra arginine or citrulline, and when the body might run short.
Traditional use
Arginine and citrulline are amino acids the body handles every day. Their normal jobs in the body are well established; that is different from showing that extra pills treat a condition.
Proposed mechanism Established physiology
Arginine is the raw material that the enzyme nitric oxide synthase uses to make nitric oxide, a molecule that helps blood vessels relax (stated in the VINTAGE MI trial abstract). Citrulline is a precursor of arginine (stated in a 2025 review).
A proposed mechanism does not show that the effect happens in people.
Arginine and citrulline can matter in illness; see the Safety tab for who should ask a clinician first.
Food sources of arginine and citrulline
High certaintyArginine comes from protein foods. By USDA data, about 1.5 g is in an ounce of pumpkin seeds, about 1.6 g in half a roasted chicken breast, about 1.0 g in a 3 oz cooked beef patty, about 1.4 g in a cup of cooked lentils and about 2.7 g in a cup of chopped walnuts. Watermelon is often named for citrulline, but USDA tables do not give a citrulline value.
2 studiesFoods only; this is not a recommendation to eat any food or to take a…
Studies, doses and limits
What the trials found
No trial was read that compares arginine from food with arginine pills for health results. USDA SR Legacy gives arginine per 100 g and per portion for common foods. It has no citrulline value for watermelon or any other food, so no citrulline amount is stated here. The watermelon arginine value is small (about 0.09 g in a cup, diced).
Results
Seeds, nuts, poultry, meat, fish, eggs and legumes all carry arginine. A cup of watermelon has very little arginine; its citrulline was not measured in the tables read.
Effect sizes as reported
USDA arginine, per 100 g and per portion: pumpkin seeds 5.35 g and about 1.52 g per oz; walnuts 2.28 g and about 2.66 g per cup chopped; chicken breast roasted 1.87 g and about 1.61 g per half breast (86 g); beef 85% lean patty broiled 1.21 g and about 1.03 g per 3 oz; Atlantic salmon farmed cooked 1.32 g and about 1.12 g per 3 oz; lentils cooked 0.70 g and about 1.38 g per cup; chickpeas cooked 0.84 g and about 1.37 g per cup; egg hard-boiled 0.76 g and about 0.38 g per large egg; watermelon raw 0.06 g and about 0.09 g per cup diced.
Why this rating
High that foods contain these amounts of arginine (USDA tables). How much of it the body absorbs from each food was not measured in the sources read, and no citrulline values were available.
Form and dose studied
Foods only; this is not a recommendation to eat any food or to take a supplement.
Who was studied
General adult diet.
Limits
SR Legacy values are from a 2018 release. Cooking and brand change amounts. Citrulline content of foods was not found in a source read.
Why researchers looked
Many people want to know where arginine and citrulline come from in food and how food compares with supplements.
Traditional use
Arginine and citrulline are amino acids the body handles every day. Their normal jobs in the body are well established; that is different from showing that extra pills treat a condition.
Proposed mechanism Nutrient database
These are nutrient amounts in foods taken from USDA tables.
A proposed mechanism does not show that the effect happens in people.
Food amounts of these amino acids are not linked to the cautions that apply to high-dose pills.
Blood pressure (arginine)
Low certaintyIn a 2022 meta-analysis of 22 placebo-controlled trials, oral arginine lowered blood pressure by a few points on average (systolic about 6 mmHg, diastolic about 3 mmHg). The effect was not seen at the highest amounts studied, in the longer trials, or in people with obesity. A 2026 meta-analysis of 5 small trials using wearable 24-hour monitors found falls of about 4 mmHg systolic and 3 mmHg diastolic.
2 studiesOral L-arginine supplements, various amounts and lengths (trial amoun…
Studies, doses and limits
What the trials found
The 2022 review pooled 22 randomised placebo-controlled trials of oral arginine in adults: systolic pressure fell by 6.40 mmHg (95% CI 8.74 to 4.05) and diastolic by 2.64 mmHg (3.94 to 1.40). Falls were seen in people with normal and high blood pressure. No significant change was seen with the highest amounts, in trials longer than 24 days, or in people with obesity. A 2026 meta-analysis of 5 trials (202 people) measuring 24-hour pressure found 24-hour systolic down 4.23 mmHg and diastolic down 3.04 mmHg, and the authors say few studies exist.
Results
Small average drops in blood pressure in trials. The effect fades in longer trials, at the highest amounts, and in people with obesity, so it is not a promise for one person.
Effect sizes as reported
2022: systolic WMD -6.40 mmHg (95% CI -8.74 to -4.05), diastolic -2.64 mmHg (-3.94 to -1.40). 2026: 24 h systolic WMD -4.23 mmHg (-5.87 to -2.58), 24 h diastolic -3.04 mmHg (-4.48 to -1.59).
Why this rating
Low: many small trials of different lengths and amounts, an effect that disappears in longer trials and in people with obesity, and only abstracts were read, so quality ratings were not seen.
Form and dose studied
Oral L-arginine supplements, various amounts and lengths (trial amounts are in the studies table).
Who was studied
Adults with normal blood pressure, high blood pressure and other health conditions.
Limits
The loss of effect at the highest amounts and in longer trials is not explained. A small average fall does not replace medical care for high blood pressure. Pregnancy is covered in the Benefits tab on its own.
Why researchers looked
Arginine makes nitric oxide, which relaxes blood vessels, so researchers tested whether arginine lowers blood pressure.
Traditional use
Arginine and citrulline are amino acids the body handles every day. Their normal jobs in the body are well established; that is different from showing that extra pills treat a condition.
Proposed mechanism Proposed mechanism
Arginine is the raw material for nitric oxide, which helps blood vessels relax. This is the proposed way it could lower blood pressure; the trials measure pressure, not the mechanism.
A proposed mechanism does not show that the effect happens in people.
Arginine may add to the effect of blood pressure medicines; no trial of that was read. See the Safety tab.
Blood pressure (citrulline and watermelon)
Low certaintyA 2025 meta-analysis of 15 trials (415 people) in middle-aged and older adults found lower blood pressure with citrulline supplements and watermelon pooled together (systolic about 4 mmHg, diastolic about 2.5 mmHg). Watermelon is a food and citrulline a pill, so the result does not show what citrulline alone does.
1 studiesL-citrulline supplements and whole watermelon; some trials combined c…
Studies, doses and limits
What the trials found
The 2025 review pooled 24 datasets from 15 trials: systolic -4.02 mmHg (95% CI -6.54 to -1.50) and diastolic -2.54 mmHg (-4.27 to -0.81). A subgroup taking citrulline together with arginine showed larger falls (systolic -10.44 mmHg), but that subgroup is small and the abstract does not separate citrulline alone from watermelon. The authors say the combination looked better than citrulline or watermelon alone.
Results
A small average drop in older adults in trials that mixed citrulline pills and watermelon. Citrulline alone was not separated out.
Effect sizes as reported
Systolic WMD -4.02 mmHg (95% CI -6.54 to -1.50); diastolic -2.54 mmHg (-4.27 to -0.81); citrulline + arginine subgroup systolic -10.44 mmHg (-13.57 to -7.31).
Why this rating
Low: 415 people in total, citrulline and watermelon pooled together, and only an abstract was read.
Form and dose studied
L-citrulline supplements and whole watermelon; some trials combined citrulline with arginine.
Who was studied
Middle-aged and older adults.
Limits
Different products were pooled. No trial in younger adults was read for this outcome.
Why researchers looked
Citrulline is turned into arginine in the body, so researchers tested whether citrulline or watermelon lowers blood pressure in older adults.
Traditional use
Arginine and citrulline are amino acids the body handles every day. Their normal jobs in the body are well established; that is different from showing that extra pills treat a condition.
Proposed mechanism Proposed mechanism
Citrulline is a precursor of arginine, which makes nitric oxide. This is the proposed route; the trials measure blood pressure.
A proposed mechanism does not show that the effect happens in people.
No harm signal was reported in the abstract; see the Safety tab for what is known.
Endurance exercise (citrulline)
Low certaintyTwo meta-analyses (9 and 10 studies) found no significant benefit from citrulline for endurance exercise in young healthy adults. One of them says repeated daily use showed a positive tendency but needs more study.
2 studiesL-citrulline, mostly single doses.
Studies, doses and limits
What the trials found
The 2023 review pooled 9 randomised trials (158 people) and found no significant difference in time to exhaustion (SMD 0.03, 95% CI -0.27 to 0.33) or time to complete an effort (SMD -0.07, -0.50 to 0.15). The 2022 review of 10 studies found no benefit for aerobic performance (SMD 0.15, -0.02 to 0.32), perceived effort, oxygen uptake or lactate.
Results
No benefit seen for endurance in young healthy adults. A trend with repeated use needs more studies.
Effect sizes as reported
2023: time to exhaustion SMD 0.03 (95% CI -0.27 to 0.33). 2022: aerobic performance SMD 0.15 (-0.02 to 0.32).
Why this rating
Low: small numbers of studies and only abstracts were read, so the lack of effect is not firmly settled either.
Form and dose studied
L-citrulline, mostly single doses.
Who was studied
Young, recreationally active healthy adults.
Limits
Women, older people and athletes at elite level were not well covered. Results do not apply to long-term daily use.
Why researchers looked
Citrulline is sold to athletes because it may raise nitric oxide and help muscles clear ammonia.
Traditional use
Arginine and citrulline are amino acids the body handles every day. Their normal jobs in the body are well established; that is different from showing that extra pills treat a condition.
Proposed mechanism Proposed mechanism
Proposed: more nitric oxide and ammonia buffering. The abstracts say this is the reason it is thought to help; the trials do not show it works.
A proposed mechanism does not show that the effect happens in people.
No specific safety signal for exercise use in the abstracts read.
Muscle strength (citrulline malate)
Low certaintyA meta-analysis of 4 small trials in resistance-trained adults found no improvement in muscle strength with citrulline malate.
1 studiesCitrulline malate (citrulline combined with malate).
Studies, doses and limits
What the trials found
The 2022 review pooled four randomised trials (138 assessments) and found no overall effect (SMD 0.13, 95% CI -0.21 to 0.46) and no difference between upper and lower limbs. The authors concluded citrulline malate does not improve strength in healthy, resistance-trained people.
Results
No strength gain seen in resistance-trained adults.
Effect sizes as reported
SMD 0.13 (95% CI -0.21 to 0.46).
Why this rating
Low: only 4 small studies; abstract only.
Form and dose studied
Citrulline malate (citrulline combined with malate).
Who was studied
Healthy, resistance-trained adults.
Limits
Few studies; no data on beginners, women or older adults in this review.
Why researchers looked
Citrulline malate is common in pre-workout products.
Traditional use
Arginine and citrulline are amino acids the body handles every day. Their normal jobs in the body are well established; that is different from showing that extra pills treat a condition.
Proposed mechanism Proposed mechanism
Proposed: nitric oxide and energy metabolism effects. The abstract calls the mechanisms well known but the strength results unclear.
A proposed mechanism does not show that the effect happens in people.
None specific in the abstract.
Muscle mass and strength (arginine and citrulline)
Mixed findingsA broad review of muscle supplements put both arginine and citrulline in the group where evidence is mixed or unclear. It also notes that some adverse events have been reported with arginine after large intakes.
1 studiesArginine and citrulline in many forms.
Studies, doses and limits
What the trials found
The 2019 review ranks supplements by evidence. Creatine, protein and polyunsaturated fats were in the group with consistent benefit. Arginine and citrulline were in the mixed or unclear group (level B). Ornithine had no evidence.
Results
Mixed or unclear evidence for muscle building.
Effect sizes as reported
Evidence level B (mixed or unclear).
Why this rating
Mixed: the review did not find consistent benefit and the evidence level is below the best-supported supplements.
Form and dose studied
Arginine and citrulline in many forms.
Who was studied
Healthy adults and people with muscle loss.
Limits
A broad narrative review, not a pooled analysis of these two amino acids; abstract only.
Why researchers looked
Both are marketed for muscle building and recovery.
Traditional use
Arginine and citrulline are amino acids the body handles every day. Their normal jobs in the body are well established; that is different from showing that extra pills treat a condition.
Proposed mechanism Proposed mechanism
Proposed: more blood flow to muscle through nitric oxide. Not shown by the review.
A proposed mechanism does not show that the effect happens in people.
Adverse events were reported with large intakes of arginine; see the Safety tab.
Erectile dysfunction (arginine)
Low certaintyTwo small meta-analyses found better sexual function scores in men with erectile dysfunction who took arginine, but the comparisons were with baseline or with a drug, or used arginine in a combination with a pine bark extract. A prescription drug of the PDE5 type worked better than arginine alone.
2 studiesDaily oral L-arginine, alone, with PDE5 inhibitors, or with Pycnogeno…
Studies, doses and limits
What the trials found
A 2021 meta-analysis of 4 trials (373 men) found sexual function improved from baseline in groups on daily arginine, a PDE5 inhibitor, or both. The drug alone did better than arginine alone, and the combination did best, without clearly more side effects than the drug alone. A 2023 meta-analysis of 3 trials (184 men with mild to moderate erectile dysfunction) found better scores with arginine plus Pycnogenol (pine bark extract) than control, with no difference in testosterone.
Results
Arginine alone improved scores from baseline but was weaker than the standard drugs. The combination with pine bark extract cannot be credited to arginine alone.
Effect sizes as reported
No numbers in the abstracts for the main scores; differences were reported as P values.
Why this rating
Low: small trials, comparisons that are not placebo-only, a combination product, and only abstracts were read.
Form and dose studied
Daily oral L-arginine, alone, with PDE5 inhibitors, or with Pycnogenol.
Who was studied
Men with erectile dysfunction.
Limits
Without a placebo-only arm, part of the improvement could be placebo effect. Erectile problems can be a sign of heart disease, so a doctor should check them.
Why researchers looked
Arginine makes nitric oxide, which widens blood vessels, and erections depend on blood flow.
Traditional use
Arginine and citrulline are amino acids the body handles every day. Their normal jobs in the body are well established; that is different from showing that extra pills treat a condition.
Proposed mechanism Proposed mechanism
Proposed: more nitric oxide. Not tested directly in the abstracts read.
A proposed mechanism does not show that the effect happens in people.
Arginine plus PDE5 drugs: no clear rise in side effects in the 2021 review. Ask a doctor or pharmacist about the combination.
Blood sugar control (arginine)
Low certaintyA meta-analysis of 12 trials found no significant effect of arginine on fasting blood sugar, insulin, HbA1c or insulin resistance. Animal studies had suggested a benefit that human trials could not confirm.
1 studiesOral L-arginine.
Studies, doses and limits
What the trials found
The 2023 review (searched to January 2020) pooled 12 randomised trials: fasting glucose WMD -3.38 mg/dl (95% CI -6.79 to 0.04), insulin -0.12, HbA1c -0.04% (-0.25 to 0.17), HOMA-IR -0.48 (-1.15 to 0.19). None was significant.
Results
No effect on blood sugar markers in 12 human trials.
Effect sizes as reported
Fasting glucose WMD -3.38 mg/dl (95% CI -6.79 to 0.04); HbA1c -0.04% (-0.25 to 0.17).
Why this rating
Low: small trials; the lack of effect is the finding, and only an abstract was read.
Form and dose studied
Oral L-arginine.
Who was studied
Adults (health status not described in the abstract).
Limits
The glucose result was close to the edge of significance (upper limit 0.04), so a small effect cannot be ruled out.
Why researchers looked
Animal studies suggested arginine might help the body handle sugar.
Traditional use
Arginine and citrulline are amino acids the body handles every day. Their normal jobs in the body are well established; that is different from showing that extra pills treat a condition.
Proposed mechanism Animal or lab
Animal work suggested an effect; human trials did not show it.
A proposed mechanism does not show that the effect happens in people.
None specific.
Pre-eclampsia in pregnancy (arginine)
Low certaintyA 2025 meta-analysis of 20 randomised trials in pregnancy found that arginine was linked to less pre-eclampsia in prevention trials, but the evidence is low-certainty and eight trials had a high risk of bias. One small citrulline study found no effect. This is a topic for a pregnancy care team, not self-treatment.
1 studiesOral L-arginine; L-citrulline in a single study.
Studies, doses and limits
What the trials found
The review pooled 20 randomised trials (2,028 women) and 3 non-randomised trials (189 women). In four prevention trials arginine was linked to less pre-eclampsia (RR 0.52, 95% CI 0.35 to 0.78) and, in three trials, less severe pre-eclampsia (RR 0.23, 0.09 to 0.55), both low-certainty. In treatment trials, arginine may lower systolic pressure (-5.64 mmHg, very low certainty) and fetal growth restriction (RR 0.46, low certainty). One citrulline study (36 women) found no effect. The authors say findings should be read cautiously.
Results
A promising but low-certainty signal for arginine; citrulline had one tiny study with no effect.
Effect sizes as reported
Prevention: pre-eclampsia RR 0.52 (0.35 to 0.78); severe RR 0.23 (0.09 to 0.55). Treatment: systolic MD -5.64 mmHg (-10.66 to -0.62).
Why this rating
Low: authors rate it low or very low certainty, with 4 or fewer trials per result and a high risk of bias in 8 of 20 trials.
Form and dose studied
Oral L-arginine; L-citrulline in a single study.
Who was studied
Pregnant women, mostly at risk of or with pre-eclampsia.
Limits
The best timing and amount are unknown. These trials were run within pregnancy care, not self-treatment.
Why researchers looked
Pre-eclampsia is high blood pressure in pregnancy, and arginine's nitric oxide role makes it a candidate.
Traditional use
Arginine and citrulline are amino acids the body handles every day. Their normal jobs in the body are well established; that is different from showing that extra pills treat a condition.
Proposed mechanism Proposed mechanism
Proposed: nitric oxide and blood vessel function in the placenta. The abstract does not test this.
A proposed mechanism does not show that the effect happens in people.
Ask a doctor or midwife before any amino acid supplement in pregnancy.
Recovery after a heart attack (arginine)
Evidence againstIn the one trial read, adding arginine after a first heart attack did not improve vessel stiffness or heart pumping, and more people on arginine died. The authors said arginine should not be recommended after a heart attack.
1 studiesL-arginine, goal of three times a day for 6 months in the trial.
Studies, doses and limits
What the trials found
The VINTAGE MI trial randomised 153 people after a first ST-segment-elevation heart attack to arginine or placebo for 6 months. There was no significant change in vessel stiffness or ejection fraction. Six people (8.6%) in the arginine group died versus none on placebo (P = .01), and the safety committee closed enrolment.
Results
No heart benefit and a death signal after a heart attack. This is evidence against use in this setting.
Effect sizes as reported
Deaths 6 (8.6%) arginine vs 0 placebo (P = .01).
Why this rating
One randomised, double-blind trial of 153 people, stopped early for safety. The death finding was not the main aim, so it is a warning signal, not a proven cause.
Form and dose studied
L-arginine, goal of three times a day for 6 months in the trial.
Who was studied
People after a first ST-segment-elevation heart attack.
Limits
One centre and one trial. It does not show the same would happen in healthy people.
Why researchers looked
Arginine was tested because it might soften stiff blood vessels and help the heart recover.
Traditional use
Arginine and citrulline are amino acids the body handles every day. Their normal jobs in the body are well established; that is different from showing that extra pills treat a condition.
Proposed mechanism Proposed mechanism
Proposed: more nitric oxide to relax vessels. The trial did not show this.
A proposed mechanism does not show that the effect happens in people.
See the Safety tab: people with heart disease should ask their cardiologist before arginine.
Connections to the rest of health
How Arginine and citrulline connects to the rest of our health knowledge graph. Every link says what kind of connection it is. A safety link (for example to the liver) is a warning, not a benefit. A study that merely mentions a topic never creates a benefit link.
Explore every connection: goals, body systems, organs, symptoms, genes
A. Wellness goals
| Connected to | Kind of connection | Evidence status | Context | Studies |
|---|---|---|---|---|
| Balanced Nutrition | High certainty | What they do in the body: Arginine is an amino acid, a building block of protein. MedlinePlus lists it as a nonessential amino acid and also as a conditionally essential one: the body usually makes enough, but may need more in illness and stress. Citrulline is a related amino acid that is not a building block of body proteins and is a precursor of arginine. Low arginine availability has been described in several illnesses. | 17 9 10 8 | |
| Balanced Nutrition | High certainty | Food sources of arginine and citrulline: Arginine comes from protein foods. By USDA data, about 1.5 g is in an ounce of pumpkin seeds, about 1.6 g in half a roasted chicken breast, about 1.0 g in a 3 oz cooked beef patty, about 1.4 g in a cup of cooked lentils and about 2.7 g in a cup of chopped walnuts. Watermelon is often named for citrulline, but USDA tables do not give a citrulline value. | 22 17 | |
| Blood Pressure Support | Low certainty | Blood pressure (arginine): In a 2022 meta-analysis of 22 placebo-controlled trials, oral arginine lowered blood pressure by a few points on average (systolic about 6 mmHg, diastolic about 3 mmHg). The effect was not seen at the highest amounts studied, in the longer trials, or in people with obesity. A 2026 meta-analysis of 5 small trials using wearable 24-hour monitors found falls of about 4 mmHg systolic and 3 mmHg diastolic. Blood pressure (citrulline and watermelon): A 2025 meta-analysis of 15 trials (415 people) in middle-aged and older adults found lower blood pressure with citrulline supplements and watermelon pooled together (systolic about 4 mmHg, diastolic about 2.5 mmHg). Watermelon is a food and citrulline a pill, so the result does not show what citrulline alone does. | 12 11 7 | |
| Heart Health | Low certainty | Blood pressure (arginine): In a 2022 meta-analysis of 22 placebo-controlled trials, oral arginine lowered blood pressure by a few points on average (systolic about 6 mmHg, diastolic about 3 mmHg). The effect was not seen at the highest amounts studied, in the longer trials, or in people with obesity. A 2026 meta-analysis of 5 small trials using wearable 24-hour monitors found falls of about 4 mmHg systolic and 3 mmHg diastolic. Blood pressure (citrulline and watermelon): A 2025 meta-analysis of 15 trials (415 people) in middle-aged and older adults found lower blood pressure with citrulline supplements and watermelon pooled together (systolic about 4 mmHg, diastolic about 2.5 mmHg). Watermelon is a food and citrulline a pill, so the result does not show what citrulline alone does. | 12 11 7 | |
| Physical Stamina | Low certainty | Endurance exercise (citrulline): Two meta-analyses (9 and 10 studies) found no significant benefit from citrulline for endurance exercise in young healthy adults. One of them says repeated daily use showed a positive tendency but needs more study. Muscle strength (citrulline malate): A meta-analysis of 4 small trials in resistance-trained adults found no improvement in muscle strength with citrulline malate. | 5 15 1 | |
| Recovery Optimization | Low certainty | Muscle strength (citrulline malate): A meta-analysis of 4 small trials in resistance-trained adults found no improvement in muscle strength with citrulline malate. | 1 | |
| Recovery Optimization | Mixed findings | Muscle mass and strength (arginine and citrulline): A broad review of muscle supplements put both arginine and citrulline in the group where evidence is mixed or unclear. It also notes that some adverse events have been reported with arginine after large intakes. | 14 | |
| Mens Vitality | Low certainty | Erectile dysfunction (arginine): Two small meta-analyses found better sexual function scores in men with erectile dysfunction who took arginine, but the comparisons were with baseline or with a drug, or used arginine in a combination with a pine bark extract. A prescription drug of the PDE5 type worked better than arginine alone. | 16 13 | |
| Libido Support | Low certainty | Erectile dysfunction (arginine): Two small meta-analyses found better sexual function scores in men with erectile dysfunction who took arginine, but the comparisons were with baseline or with a drug, or used arginine in a combination with a pine bark extract. A prescription drug of the PDE5 type worked better than arginine alone. | 16 13 | |
| Blood Sugar Balance | Low certainty | Blood sugar control (arginine): A meta-analysis of 12 trials found no significant effect of arginine on fasting blood sugar, insulin, HbA1c or insulin resistance. Animal studies had suggested a benefit that human trials could not confirm. | 6 | |
| Metabolic Health | Low certainty | Blood sugar control (arginine): A meta-analysis of 12 trials found no significant effect of arginine on fasting blood sugar, insulin, HbA1c or insulin resistance. Animal studies had suggested a benefit that human trials could not confirm. | 6 | |
| Womens Wellness | Low certainty | Pre-eclampsia in pregnancy (arginine): A 2025 meta-analysis of 20 randomised trials in pregnancy found that arginine was linked to less pre-eclampsia in prevention trials, but the evidence is low-certainty and eight trials had a high risk of bias. One small citrulline study found no effect. This is a topic for a pregnancy care team, not self-treatment. | 8 | |
| Heart Health | Evidence against | Recovery after a heart attack (arginine): In the one trial read, adding arginine after a first heart attack did not improve vessel stiffness or heart pumping, and more people on arginine died. The authors said arginine should not be recommended after a heart attack. | 10 |
B. Body systems
| Connected to | Kind of connection | Evidence status | Context | Studies |
|---|---|---|---|---|
| Whole Body | Biological association | High certainty | Studied for: What they do in the body | 17 9 10 8 |
| Cardiovascular System | Biological association | High certainty | Studied for: What they do in the body Studied for: Blood pressure (arginine) | 17 9 10 8 12 11 7 5 15 16 13 |
| Nutrition | Biological association | High certainty | Studied for: Food sources of arginine and citrulline | 22 17 |
| Digestive System | Biological association | High certainty | Studied for: Food sources of arginine and citrulline | 22 17 |
| Heart Circulation | Biological association | Low certainty | Studied for: Blood pressure (arginine) Studied for: Blood pressure (citrulline and watermelon) | 12 11 7 |
| Musculoskeletal System | Biological association | Low certainty | Studied for: Endurance exercise (citrulline) Studied for: Muscle strength (citrulline malate) | 5 15 1 14 |
| Reproductive System | Biological association | Low certainty | Studied for: Erectile dysfunction (arginine) Studied for: Pre-eclampsia in pregnancy (arginine) | 16 13 8 |
| Endocrine System | Biological association | Low certainty | Studied for: Blood sugar control (arginine) | 6 |
E. Health conditions
| Connected to | Kind of connection | Evidence status | Context | Studies |
|---|---|---|---|---|
| Heart attack (myocardial infarction) | Adverse effect or risk | Documented risk | More deaths on arginine than placebo in one trial after a first heart attack. Preparation or compound: L-arginine |
10 |
| High blood pressure | Preliminary | Small average falls in blood pressure in meta-analyses; low certainty. Small average blood pressure falls in meta-analyses; low certainty. Preparation or compound: L-arginine; citrulline and watermelon |
12 11 7 | |
| Pre-eclampsia | Preliminary | Less pre-eclampsia with arginine in four prevention trials; low certainty. Preparation or compound: L-arginine |
8 |
I. Biomarkers
| Connected to | Kind of connection | Evidence status | Context | Studies |
|---|---|---|---|---|
| Systolic blood pressure (top number) | Biological association | Low certainty | Measured in trials: lower (small average fall). A lab change is not the same as a health benefit. | 12 11 7 |
| Diastolic blood pressure (bottom number) | Biological association | Low certainty | Measured in trials: lower (small average fall). A lab change is not the same as a health benefit. | 12 11 7 |
| 24-hour (ambulatory) blood pressure | Biological association | Low certainty | Measured in trials: lower. A lab change is not the same as a health benefit. | 11 |
| Fasting glucose, HbA1c and insulin resistance | Biological association | Low certainty | Measured in trials: no significant change. A lab change is not the same as a health benefit. | 6 |
| Time to exhaustion and time to complete an effort | Biological association | Low certainty | Measured in trials: no significant change. A lab change is not the same as a health benefit. | 5 |
| Pre-eclampsia | Biological association | Low certainty | Measured in trials: lower risk in prevention trials (low certainty). A lab change is not the same as a health benefit. | 8 |
J. Genes, receptors and enzymes
| Connected to | Kind of connection | Evidence status | Context | Studies |
|---|---|---|---|---|
| ARG1 (arginase) | Preliminary mechanism | Human | Arginase deficiency, caused by variants in the ARG1 gene, makes arginine and ammonia build up in the blood (MedlinePlus Genetics). | 18 |
K. Biological pathways
L. Active compounds
| Connected to | Kind of connection | Evidence status | Context | Studies |
|---|---|---|---|---|
| L-arginine | Biological association | Human | Substrate for nitric oxide synthase (VINTAGE MI trial abstract); tested for blood pressure, erectile function, blood sugar, pre-eclampsia and after a heart attack. | 10 12 16 6 8 |
| L-citrulline | Biological association | Human | A precursor of arginine (2025 review); tested for blood pressure (pooled with watermelon) and endurance. | 8 7 5 |
| Citrulline malate | Biological association | Human | Citrulline combined with malate; tested for muscle strength in resistance-trained adults. | 1 |
| Arginine monohydrochloride | Biological association | Human | The form given into a vein in the 1978 potassium case report; not a supplement form. | 2 |
Each connection is stored with the ingredient, the connected record, the kind of connection, the evidence status, the supporting studies, the preparation or compound involved, and a review date (last reviewed October 26, 2026).
Evidence at a glance: what the research found for 11 outcomes
Each outcome below is one thing researchers measured. Certainty is how far the evidence can be trusted, not how well it works. The full studies are on the next tab.
The evidence
The research centre for Arginine and citrulline. Every record here was checked against PubMed or the publisher's page; we never list a study we have not verified.
Evidence by outcome
Bars show how many studies we found for each outcome, not how well it works. People are added up across trials only (reviews are not added, to avoid double counting).
How we rate evidence
High certainty
Several well-run trials or reviews agree; further research is unlikely to change the picture much.
Moderate certainty
Good trials point the same way, but some doubt remains.
Low certainty
Small, short or inconsistent trials. The finding could change with better research.
Very low certainty
Very little or very weak human data. Treat as a possibility only.
Mixed findings
Trials or reviews disagree with each other.
Not enough evidence
Not enough human research to say either way.
Evidence against
Good research found no benefit, or found harm.
We take the reviewers' own risk-of-bias and GRADE statements where they exist, and otherwise judge from study size, design, consistency, directness and whether a product matches what is sold. Many publications do not make evidence high. Method note: We started from our existing amino acid summary, read MedlinePlus pages, re-checked food values in saved USDA FoodData Central data, and re-read PubMed abstracts for reviews, trials and a case report. Only abstracts were read for studies. The NIH Office of Dietary Supplements site was blocked and is marked unread.
Study library: every study we checked 22
| Study | Design | People | Product, dose, length | Result |
|---|---|---|---|---|
| Aguiar 2022 Effects of Citrulline Malate Supplementation on Muscle Strength in Resistance-Trained Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Diet Suppl · PMID 34176406 · DOI |
Systematic review meta analysis |
138 4 randomised trials, 138 assessments (69 citrulline malate, 69 placebo), resistance-trained adults |
Citrulline malate Oral Not given in the abstract Not given in the abstract · vs Placebo |
No overall effect on muscle strength, and no difference between upper and lower limbs. The authors concluded citrulline malate does not improve muscle strength in healthy, resistance-trained people. Overall SMD 0.13 (-0.21 to 0.46) Methods, limits and fundingOutcomes: Muscle strength in resistance exercise Limitations: Only 4 small studies; searched two databases to August 2020. Read from the abstract only. Funding and conflicts: The abstract does not state funding or conflicts of interest. Registration: PROSPERO CRD42020159338 Read: abstract |
| Bushinsky 1978 Life-threatening hyperkalemia induced by arginine. Ann Intern Med · PMID 717931 · DOI |
Case report |
2 Two patients with severe liver disease and moderate kidney weakness who had recently had spironolactone |
Arginine monohydrochloride infusion (into a vein, not a supplement) Intravenous During and just after the infusion |
Marked high potassium (hyperkalaemia) during and after the infusion; in one patient it came with a fatal heart rhythm problem. Arginine is known to move potassium out of cells, and the patients could not clear it. The authors advise caution in people with kidney or liver weakness. Two cases (Not applicable) Methods, limits and fundingOutcomes: Blood potassium Limitations: A 1978 report of intravenous arginine in two very sick people. It does not show the same happens with arginine pills in healthy people. Read from the abstract only. Funding and conflicts: Not stated. Read: abstract |
| Davani-Davari 2019 The Renal Safety of L-Carnitine, L-Arginine, and Glutamine in Athletes and Bodybuilders. J Ren Nutr · PMID 30341034 · DOI |
Narrative review |
Review of 7 studies of L-arginine (and others for carnitine and glutamine) in athletes and bodybuilders; searched to December 2017 | L-arginine Oral Routine amounts in the studies ranged from 3 g to more than 100 g a day (review's wording; trial amounts, not advice) Varied |
Arginine appears to have both beneficial and detrimental effects on kidney function, but adverse effects are unlikely to occur with the routine amounts studied in athletes. The review says more clinical data are needed. No numbers in the abstract (Not applicable) Methods, limits and fundingOutcomes: Kidney function and kidney injury Limitations: Covers athletes and bodybuilders with healthy kidneys, not people with kidney disease. Read from the abstract only. Funding and conflicts: The abstract does not state funding or conflicts. Read: abstract |
| Elango 2023 Tolerable Upper Intake Level for Individual Amino Acids in Humans: A Narrative Review of Recent Clinical Studies. Adv Nutr · PMID 37062432 · DOI |
Narrative review |
Review of human safety studies of 10 amino acids, including arginine and citrulline, in relatively healthy adults | Single amino acids including L-arginine and L-citrulline Oral No-observed-adverse-effect level: arginine 30 g a day; citrulline 24 g a day (study findings, not advice) Short-term dose-finding studies |
The review says that no national health agency has set an upper intake level for amino acids because well-run human dose studies were lacking. In relatively healthy adults the tested amino acids were well tolerated, and the review proposed no-observed-adverse-effect levels for arginine and citrulline. It calls these a first set of data for agencies. NOAEL arginine 30 g/day; citrulline 24 g/day (Not applicable) Methods, limits and fundingOutcomes: Tolerance and the highest amounts with no observed harm Limitations: A narrative review of short studies in relatively healthy adults, not of long-term use, children, pregnancy or illness. These are not official limits. Read from the abstract only. Funding and conflicts: Abstract says the studies were conducted under an initiative of the International Council on Amino Acid Science, a nonprofit organisation. Who funds that body is not stated in the abstract, so do not treat these studies as independent without checking. Read: abstract |
| Harnden 2023 Effects of citrulline on endurance performance in young healthy adults: a systematic review and meta-analysis. J Int Soc Sports Nutr · PMID 37155582 · DOI |
Systematic review meta analysis |
158 9 randomised trials (158 people), young healthy adults who were at least recreationally active |
L-citrulline Oral, single dose or loading Not given in the abstract Acute (single or short loading) · vs Placebo or control |
No significant difference in endurance with citrulline compared with control. The authors say the evidence base is small. Time to exhaustion SMD 0.03; time to completion SMD -0.07 (Time to exhaustion -0.27 to 0.33; time to completion -0.50 to 0.15) Methods, limits and fundingOutcomes: Time to exhaustion (5 studies) and time to complete a set effort (4 studies) Limitations: Small number of studies; single doses mostly; young healthy people only. Read from the abstract only. Funding and conflicts: Authors report no conflict of interest. Read: abstract |
| Karimi 2023 Effects of L-arginine supplementation on biomarkers of glycemic control: a systematic review and meta-analysis of randomised clinical trials. Arch Physiol Biochem · PMID 33426939 · DOI |
Systematic review meta analysis |
12 randomised trials in adults; searched to January 2020 | L-arginine Oral Not given in the abstract Not given in the abstract · vs Placebo or control |
No significant effect on fasting blood sugar, insulin, HbA1c or insulin resistance. The authors say animal studies had suggested a benefit but this could not be confirmed in humans. Fasting glucose WMD -3.38 mg/dl; insulin -0.12; HbA1c -0.04%; HOMA-IR -0.48 (Glucose -6.79 to 0.04; HbA1c -0.25 to 0.17; HOMA-IR -1.15 to 0.19) Methods, limits and fundingOutcomes: Fasting blood sugar, insulin, HbA1c, insulin resistance (HOMA-IR) Limitations: Small trials; populations not described in the abstract. Read from the abstract only. Funding and conflicts: The abstract does not state funding or conflicts. Read: abstract |
| Luo 2025 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 · PMID 40789388 · DOI |
Systematic review meta analysis |
415 15 randomised trials (24 datasets, 415 people) in middle-aged and older adults |
L-citrulline supplements and watermelon (analysed together); a subgroup used citrulline plus arginine Supplement or whole watermelon Not given in the abstract Not given in the abstract · vs Not described in the abstract |
Citrulline supplements and watermelon together lowered systolic pressure by 4.02 mmHg and diastolic by 2.54 mmHg. A subgroup that took citrulline together with arginine showed larger falls (systolic -10.44 mmHg). The effect of citrulline alone is not separated out in the abstract. Systolic -4.02 mmHg; diastolic -2.54 mmHg; citrulline + arginine subgroup systolic -10.44 mmHg (Systolic -6.54 to -1.50; diastolic -4.27 to -0.81) Methods, limits and fundingOutcomes: Systolic and diastolic blood pressure Limitations: Citrulline and watermelon were pooled, so this does not show what citrulline alone does. Small total numbers. Read from the abstract only. Funding and conflicts: Authors state no conflict of interest. Read: abstract |
| Makama 2025 L-Arginine and L-Citrulline for Prevention and Treatment of Pre-Eclampsia: A Systematic Review and Meta-Analysis. BJOG · PMID 39800868 · DOI |
Systematic review meta analysis |
2028 20 randomised trials (2,028 pregnant women) and 3 non-randomised trials (189 women); searched to February 2024 |
L-arginine (and L-citrulline in one trial) Oral Not given in the abstract Not given in the abstract · vs Placebo or standard care |
In four prevention trials, arginine was linked to less pre-eclampsia and, in three, less severe pre-eclampsia (both low-certainty). In treatment trials, arginine may lower systolic pressure (very low certainty) and fetal growth restriction (low certainty). One small citrulline study (36 women) found no effect. Risk of bias was high in 8 of the 20 randomised trials. Prevention: pre-eclampsia RR 0.52; severe pre-eclampsia RR 0.23. Treatment: systolic MD -5.64 mmHg; growth restriction RR 0.46 (Pre-eclampsia 0.35 to 0.78; severe 0.09 to 0.55; systolic -10.66 to -0.62; growth restriction 0.26 to 0.81) Methods, limits and fundingOutcomes: Pre-eclampsia, severe pre-eclampsia, blood pressure, fetal growth restriction Limitations: Few trials per result; high or uncertain risk of bias; low or very low certainty by the authors. Optimal timing and amount unknown. Read from the abstract only. Funding and conflicts: Authors declare no conflicts of interest. Read: abstract |
| Morris 2017 Acquired Amino Acid Deficiencies: A Focus on Arginine and Glutamine. Nutr Clin Pract · PMID 28388380 · DOI |
Narrative review |
Review of conditions in which arginine or glutamine become low | Arginine and glutamine (as nutrients) |
Arginine and glutamine are conditionally essential: usually made by the body, but needed from outside in stress and illness. Low arginine availability is described in sickle cell disease, thalassaemia, malaria, acute asthma, cystic fibrosis, pulmonary hypertension, cardiovascular disease, some cancers and trauma. Breakdown by arginase enzymes is the most common cause. The abstract describes this as a role in disease, not a trial result. No numbers in the abstract (Not applicable) Methods, limits and fundingOutcomes: Why arginine becomes low in illness Limitations: Describes an association with illness; the abstract does not give trial results showing that supplements treat any of these conditions. Read from the abstract only. Funding and conflicts: The abstract does not state funding or conflicts. Read: abstract |
| Schulman 2006 L-arginine therapy in acute myocardial infarction: the Vascular Interaction With Age in Myocardial Infarction (VINTAGE MI) randomized clinical trial. JAMA · PMID 16391217 · DOI |
Randomised controlled trial |
153 153 people after a first ST-segment-elevation heart attack (mean age 60); 77 were aged 60 or over |
L-arginine Capsule or powder (form not stated in the abstract) Goal 3 g three times a day (trial amount, not advice) 6 months · vs Matching placebo |
No change in vessel stiffness or ejection fraction in either group. 6 people (8.6%) in the arginine group died during the 6 months versus none on placebo. The safety committee closed enrolment. The authors concluded arginine should not be recommended after a heart attack. Deaths: 6 (8.6%) arginine versus 0 placebo, P = .01 (Not given in the abstract) Methods, limits and fundingOutcomes: Heart pumping ability (ejection fraction), blood vessel stiffness, deaths Limitations: One centre; the main aim was vessel stiffness and heart function, not deaths, so the death finding was a safety signal seen in a trial that stopped early. Applies to people after a heart attack, not to healthy adults. Funding and conflicts: Listed as NIH-supported research. Conflicts of interest are not stated in the abstract. Registration: NCT00051376 Read: abstract |
| Shi 2026 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 · PMID 42520885 · DOI |
Systematic review meta analysis |
202 5 randomised trials (202 people) that measured blood pressure over 24 hours with a wearable monitor; searched to March 2026 |
Oral L-arginine Oral supplement Not given in the abstract Not given in the abstract · vs Control (placebo or no arginine; not detailed in the abstract) |
24-hour systolic pressure was 4.23 mmHg lower and diastolic 3.04 mmHg lower. Daytime and night-time readings were also lower. The authors say the number of studies was small and more are needed. 24 h systolic WMD -4.23 mmHg; 24 h diastolic WMD -3.04 mmHg; night systolic -5.70 mmHg (24 h systolic -5.87 to -2.58; 24 h diastolic -4.48 to -1.59) Methods, limits and fundingOutcomes: 24-hour, daytime and night-time systolic and diastolic pressure Limitations: Only 5 small trials. Read from the abstract only; the population (healthy or with high blood pressure) is not described there. Funding and conflicts: Authors state no conflicts of interest. Read: abstract |
| Shiraseb 2022 Effect of l-Arginine Supplementation on Blood Pressure in Adults: A Systematic Review and Dose-Response Meta-analysis of Randomized Clinical Trials. Adv Nutr · PMID 34967840 · DOI |
Systematic review meta analysis |
22 randomised placebo-controlled trials (30 effect sizes) of oral L-arginine in adults; searched to April 2021 | Oral L-arginine Oral supplement Trials differed; no clear effect was seen with amounts above 9 g a day, and an effect was seen from about 4 g a day for systolic pressure (trial amounts, not advice) At least 4 days · vs Placebo |
Systolic pressure fell by 6.40 mmHg and diastolic by 2.64 mmHg on average. Falls were seen in people with normal and high blood pressure. No significant change was seen with the highest amounts, in trials longer than 24 days, or in people with obesity. Diastolic pressure fell more in women than men. Systolic WMD -6.40 mmHg; diastolic WMD -2.64 mmHg (Systolic -8.74 to -4.05; diastolic -3.94 to -1.40) Methods, limits and fundingOutcomes: Systolic and diastolic blood pressure Limitations: Read from the abstract only. Quality ratings of the trials and heterogeneity are not in the abstract. The loss of effect in longer trials and the highest amounts makes the average hard to apply to one person. Funding and conflicts: The abstract does not state funding. No conflicts of interest are stated in the abstract. Registration: PROSPERO CRD42021242772 Read: abstract |
| Tian 2023 Efficacy of L-arginine and Pycnogenol in the treatment of male erectile dysfunction: a systematic review and meta-analysis. Front Endocrinol · PMID 37908749 · DOI |
Systematic review meta analysis |
184 3 trials (184 men) with mild to moderate erectile dysfunction |
L-arginine combined with Pycnogenol (pine bark extract) Oral Not given in the abstract Not given in the abstract · vs Control (not detailed in the abstract) |
The combination improved erectile function, intercourse satisfaction, orgasm, overall satisfaction and desire scores compared with control. Testosterone did not differ. Because it is a combination, the result does not show what arginine alone does. Significant differences in sexual function scores (numbers not in the abstract) (Not given in the abstract) Methods, limits and fundingOutcomes: Erectile function, satisfaction, desire, testosterone Limitations: Combination product, three small trials. Read from the abstract only. Funding and conflicts: Authors state no commercial or financial relationships. Registration: PROSPERO CRD42023411781 Read: abstract |
| Valenzuela 2019 Supplements with purported effects on muscle mass and strength. Eur J Nutr · PMID 30604177 · DOI |
Narrative review |
Review of many popular muscle supplements | Many supplements, including arginine and citrulline Oral |
Arginine and citrulline were placed in the group with mixed or unclear evidence (level B). The review notes that some adverse events were reported with several supplements, arginine among them, after large intakes. Evidence level B (mixed or unclear) (Not applicable) Methods, limits and fundingOutcomes: Evidence level for muscle mass or strength Limitations: A broad review, not a pooled analysis of arginine or citrulline. Read from the abstract only. Funding and conflicts: The abstract does not state funding or conflicts. Read: abstract |
| Viribay 2022 Effects of Citrulline Supplementation on Different Aerobic Exercise Performance Outcomes: A Systematic Review and Meta-Analysis. Nutrients · PMID 36079738 · DOI |
Systematic review meta analysis |
10 studies comparing citrulline with placebo on aerobic exercise | L-citrulline Oral Not given in the abstract Varied · vs Placebo |
No benefit for aerobic performance, perceived effort, oxygen uptake or lactate. The authors say chronic (repeated) use showed a positive tendency and more studies are needed. Aerobic performance SMD 0.15; effort -0.03; oxygen uptake 0.01; lactate 0.25 (Performance -0.02 to 0.32; effort -0.43 to 0.38; oxygen uptake -0.16 to 0.17; lactate -0.10 to 0.59) Methods, limits and fundingOutcomes: Aerobic performance, perceived effort, oxygen uptake, lactate Limitations: Only 10 studies; read from the abstract only. Funding and conflicts: Authors affirm no conflict of interest. Read: abstract |
| Xu 2021 Comparison of efficacy and safety of daily oral L-arginine and PDE5Is alone or combination in treating erectile dysfunction: A systematic review and meta-analysis of randomised controlled trials. Andrologia · PMID 33587304 · DOI |
Systematic review meta analysis |
373 4 randomised trials (373 men) with erectile dysfunction |
Daily oral L-arginine, alone or with a PDE5 inhibitor (the drug class that includes sildenafil) Oral Not given in the abstract Not given in the abstract · vs PDE5 inhibitor alone, or arginine alone |
Sexual function improved from baseline in all three treatment groups. The drug alone worked better than arginine alone. Arginine plus the drug did better than either alone, with no clear increase in side effects compared with the drug alone. Differences reported as P values (e.g. combination vs drug alone, sexual function P = 0.005) (Not given in the abstract) Methods, limits and fundingOutcomes: Sexual function score, total testosterone, side effects Limitations: Compared groups with each other and with baseline, not with a placebo-only group, so improvement from baseline may include placebo effect. Small trials. Read from the abstract only. Funding and conflicts: The abstract does not state funding or conflicts. Read: abstract |
| s-medlineplus-aminoacids MedlinePlus Medical Encyclopedia: Amino acids (review date 2025-01-21) · Source |
Reference database n/a |
Methods, limits and fundingRead: full-text | ||
| s-medlineplus-arginase MedlinePlus Genetics: Arginase deficiency (last updated 2024-02-13) · Source |
Reference database n/a |
Methods, limits and fundingRead: full-text | ||
| s-medlineplus-citrullinemia MedlinePlus Genetics: Citrullinemia (last updated 2017-05-01) · Source |
Reference database n/a |
Methods, limits and fundingRead: full-text | ||
| s-medlineplus-supplements MedlinePlus: Herbs and Supplements A-Z list · Source |
Reference database n/a |
Methods, limits and fundingRead: full-text | ||
| s-ods-arginine NIH Office of Dietary Supplements fact sheets · Source |
Reference database n/a |
Methods, limits and fundingRead: not-read | ||
| s-usda-sr-legacy-arginine USDA FoodData Central, SR Legacy (April 2018 release): arginine in foods · Source |
Reference database n/a |
Methods, limits and fundingRead: full-text |
What we do not know yet
- No trial was read showing extra arginine or citrulline helps healthy, well-fed adults.
- Citrulline alone was not separated from watermelon in the blood pressure review.
- No trial of the amino acids taken with blood pressure or nitrate medicines was read.
- The NIH Office of Dietary Supplements could not be read (blocked), and no agency upper limit was confirmed.
- No safety data were read for breastfeeding or children, and contamination and label accuracy were not researched.
- Citrulline content of foods was not found.
How new research is added
New studies are found by a saved PubMed search and placed in a review queue before the page changes.
Lab markers
What changed in blood or saliva tests during trials. A changed number is not the same as feeling or being healthier, and we give no "normal ranges".
Other 6
Systolic blood pressure (top number)
Lower (small average fall) in trials
The pressure in your arteries when the heart beats. It is the first or top number.
Low certaintyResults and what it means
Why it was measured
To see whether arginine or citrulline lowers the top blood pressure number.
Statistical vs. clinical meaning
Small average falls in pooled trials; the effect fades in longer trials and with higher amounts for arginine.
Safety implication
Could add to the effect of blood pressure medicines; ask a doctor or pharmacist.
| Study | Result | People | Product |
|---|---|---|---|
| 12 | WMD -6.40 mmHg (95% CI -8.74 to -4.05) | 22 placebo-controlled trials in adults | Oral L-arginine |
| 11 | 24-hour systolic WMD -4.23 mmHg (95% CI -5.87 to -2.58) | 5 trials, 202 people, wearable 24-hour monitors | Oral L-arginine |
| 7 | WMD -4.02 mmHg (95% CI -6.54 to -1.50) | 15 trials, 415 middle-aged and older adults | L-citrulline supplements and watermelon pooled |
Diastolic blood pressure (bottom number)
Lower (small average fall) in trials
The pressure in your arteries between heart beats. It is the second or bottom number.
Low certaintyResults and what it means
Why it was measured
To see whether arginine or citrulline lowers the bottom blood pressure number.
Statistical vs. clinical meaning
Small average falls in pooled trials.
Safety implication
Same as systolic.
| Study | Result | People | Product |
|---|---|---|---|
| 12 | WMD -2.64 mmHg (95% CI -3.94 to -1.40) | 22 placebo-controlled trials in adults | Oral L-arginine |
| 11 | 24-hour diastolic WMD -3.04 mmHg (95% CI -4.48 to -1.59) | 5 trials, 202 people | Oral L-arginine |
| 7 | WMD -2.54 mmHg (95% CI -4.27 to -0.81) | 15 trials, 415 middle-aged and older adults | L-citrulline supplements and watermelon pooled |
24-hour (ambulatory) blood pressure
Lower in trials
Blood pressure recorded repeatedly over a full day and night with a wearable monitor, rather than once in a clinic.
Low certaintyResults and what it means
Why it was measured
A wearable monitor gives a fuller picture than clinic readings, which can be affected by nerves.
Statistical vs. clinical meaning
Only five small trials; the authors say more are needed.
Safety implication
Same as systolic.
| Study | Result | People | Product |
|---|---|---|---|
| 11 | Night-time systolic WMD -5.70 mmHg (95% CI -7.81 to -3.58); night-time diastolic -4.18 mmHg (-6.27 to -2.09); daytime systolic -4.16 mmHg | 5 trials, 202 people | Oral L-arginine |
Fasting glucose, HbA1c and insulin resistance
No significant change in trials
Fasting glucose is blood sugar after not eating. HbA1c reflects average blood sugar over about three months. HOMA-IR estimates insulin resistance.
Low certaintyResults and what it means
Why it was measured
To see whether arginine changes blood sugar control.
Statistical vs. clinical meaning
No significant effect.
Safety implication
People on diabetes medicines should ask before adding supplements.
| Study | Result | People | Product |
|---|---|---|---|
| 6 | Fasting glucose WMD -3.38 mg/dl (95% CI -6.79 to 0.04); HbA1c -0.04% (-0.25 to 0.17); HOMA-IR -0.48 (-1.15 to 0.19) | 12 randomised trials in adults | Oral L-arginine |
Time to exhaustion and time to complete an effort
No significant change in trials
How long someone can keep exercising at a steady effort, or how long a set effort takes to finish.
Low certaintyResults and what it means
Why it was measured
To see whether citrulline improves endurance.
Statistical vs. clinical meaning
No significant effect.
Safety implication
None specific.
| Study | Result | People | Product |
|---|---|---|---|
| 5 | Time to exhaustion SMD 0.03 (95% CI -0.27 to 0.33); time to completion SMD -0.07 (-0.50 to 0.15) | 9 trials, 158 young healthy adults | L-citrulline |
Pre-eclampsia
Lower risk in prevention trials (low certainty) in trials
A pregnancy condition with high blood pressure that can harm mother and baby.
Low certaintyResults and what it means
Why it was measured
To see whether arginine lowers the chance of pre-eclampsia.
Statistical vs. clinical meaning
Low-certainty signal; trials had a high risk of bias.
Safety implication
Pregnancy needs care-team advice.
| Study | Result | People | Product |
|---|---|---|---|
| 8 | Pre-eclampsia RR 0.52 (95% CI 0.35 to 0.78); severe RR 0.23 (0.09 to 0.55) | Pregnant women in 4 and 3 prevention trials | L-arginine |
Safety
What studies and official sources say about side effects, medicines and who should check first. Each point shows what kind of evidence it comes from.
Main points to know 4
- Not after a heart attack: more deaths on arginine in one trial. In a 6-month trial of 153 people after a first heart attack, 6 people (8.6%) taking arginine died versus none on placebo. The safety committee stopped enrolment, and the authors concluded arginine should not be recommended after a heart attack. Arginine did not improve vessel stiffness or heart function in that trial. If you have heart disease or have had a heart attack, ask your cardiologist before taking arginine. Randomised controlled trial 10
- Kidney or liver weakness and potassium: a warning from case reports. A 1978 report described two very sick people with severe liver disease and moderate kidney weakness who developed dangerously high potassium during and after arginine given into a vein; one had a fatal heart rhythm problem. Both had recently taken spironolactone. The authors advise caution in people with kidney or liver weakness. This was intravenous arginine, not pills, so how far it applies to supplements is not known. Case report 2 3
- Blood pressure could drop too low if combined with blood pressure medicines. Arginine lowered blood pressure in pooled trials, and citrulline with watermelon did too. No trial of arginine or citrulline taken with blood pressure medicines was read, so the size of any added effect is unknown. If you take medicines for blood pressure or heart disease, ask a doctor or pharmacist first. Inference from meta analyses (not tested as a combination) 12 11 7
- Inherited conditions where arginine or ammonia build up. In arginase deficiency (very rare, about 1 in 300,000 to 1,000,000) arginine and ammonia gradually build up in the blood. In citrullinemia (type I about 1 in 57,000 worldwide) ammonia and other toxic substances build up. People with these conditions are managed by a specialist team. Whether extra arginine or citrulline pills are safe in them was not shown in the sources read, so they should ask their metabolic specialist first. Authoritative guidance (condition descriptions); the supplement advice is an inference 18 19
Side effects 4
| Effect | How often | Severity and recovery | Evidence |
|---|---|---|---|
| Adverse events reported after large intakes of arginine The abstract does not list which events. Specific events such as stomach upset were not confirmed in a source read. | No frequency given. A 2019 review says some adverse events have been reported with several supplements, arginine among them, after large intakes. | Not described in the abstract Not described in the sources read. | Narrative review 14 |
| Well tolerated in short studies of relatively healthy adults Short studies in relatively healthy adults only. The studies were run under an initiative of a nonprofit amino acid science council, whose funders are not named in the abstract. These are not official limits. | A 2023 review of dose-finding studies says the tested amino acids, arginine and citrulline included, were well tolerated in relatively healthy adults, and proposed no-observed-adverse-effect levels. | No adverse effect at the tested levels (per the review) Not applicable | Narrative review 4 |
| Death signal after a heart attack The deaths were a safety finding in a trial that was not designed to count deaths. | 6 people (8.6%) in the arginine group died in 6 months versus none on placebo (P = .01). | Fatal Not applicable | Randomised controlled trial 10 |
| Possible mixed effects on kidney function The review says adverse effects are unlikely with the routine amounts studied in athletes. That covers athletes with healthy kidneys, not people with kidney disease. | A 2019 review of athletes and bodybuilders says arginine appears to have both beneficial and detrimental effects on kidney function. | Not described in the abstract Not described in the sources read. | Narrative review 3 |
Liver
No liver injury from arginine or citrulline was found in the sources read. A liver-safety reference (LiverTox) was not opened for this page. The 1978 case report involved people who already had severe liver disease. 2
How often. No frequency was found.
Monitoring. No agency monitoring advice was found.
This is a safety connection. It is not evidence that Arginine and citrulline supports liver health.
Medicines and supplements 5
| With | Why it matters | Importance | Evidence | What to do |
|---|---|---|---|---|
| Blood pressure medicines (any type) prescription | Arginine and citrulline can lower blood pressure in trials, which could add to a medicine's effect. | No trial of the combination was read. The possible extra drop is inferred from the blood pressure results, not measured. | Inference from meta analyses Not enough evidence 12 11 7 | Ask a doctor or pharmacist before combining. |
| PDE5 inhibitors for erectile dysfunction (the drug class that includes sildenafil) prescription | Both work through blood vessel relaxation. | A 2021 meta-analysis of 4 trials found that arginine plus a PDE5 inhibitor did not clearly increase side effects compared with the drug alone, and improved sexual function scores more than either alone. | Meta-analysis Low certainty 16 | Ask a doctor or pharmacist before combining. |
| Nitrate medicines for angina (such as nitroglycerin) prescription | Both act on the nitric oxide pathway, so an added effect on blood pressure is possible. | No source read tested this. It is a possibility, not a finding. | Inference (no source read) Not enough evidence 10 | Ask a doctor or pharmacist before combining. |
| Spironolactone and other medicines that raise potassium prescription | Arginine is known to shift potassium out of cells (stated in a 1978 case report). With kidney or liver weakness this can leave potassium too high. | The report involved intravenous arginine in two very sick people who had recently taken spironolactone, and one death. It does not show that pills do this in healthy people. | Case report Very low certainty 2 | Ask a doctor or pharmacist, especially with kidney or liver problems. |
| Medicines for diabetes prescription | No interaction with diabetes medicines was read. | Meta analysis (no interaction data) Not enough evidence 6 | Tell your diabetes team about any supplement. |
Who should check first 6
| Situation | Advice | Evidence |
|---|---|---|
| After a heart attack or with heart disease | One trial after a first heart attack found more deaths on arginine, and its authors advised against use. Heart disease patients should ask their cardiologist before taking arginine. | Randomised controlled trial 10 |
| Kidney disease or liver disease | A case report of high potassium involved severe liver disease with kidney weakness. A review of arginine's kidney safety covered athletes only. Ask a doctor first. | Case report and review 2 3 |
| Pregnancy | Trials of arginine in pregnancy were run within pregnancy care, mostly for pre-eclampsia, with low or very low certainty results and a high risk of bias in some trials. Do not start an amino acid supplement in pregnancy without your doctor or midwife. | Meta-analysis 8 |
| Breastfeeding | No source read gave safety information for arginine or citrulline during breastfeeding. Ask a doctor or pharmacist. | No data found |
| Children | No trial in children was read for either amino acid. Do not give a child arginine or citrulline supplements without a doctor's advice. | No data found |
| Inherited urea cycle disorders (arginase deficiency, citrullinemia) | In these conditions arginine, citrulline or ammonia levels can build up. Ask the specialist team before any supplement. | Authoritative guidance (condition descriptions) plus inference 18 19 |
Overdose, product quality and regulators
Summary. Short studies in relatively healthy adults found arginine and citrulline well tolerated. Harm has been reported after a heart attack and in very sick people with kidney or liver weakness.
Animal. Not reviewed.
High dose or long term signals. A 2019 review noted adverse events after large intakes of arginine. The blood pressure meta-analysis found the effect disappeared at the highest amounts and in longer trials. No long-term safety trial was read.
Overdose response. No overdose information was found in the sources read. If someone has taken a large amount and feels unwell, call poison control or emergency services.
Genotoxicity. Not researched.
Contamination and label accuracy of arginine and citrulline products were not researched for this page.
Many products mix ingredients. Citrulline is often sold as citrulline malate, and arginine and citrulline appear in pre-workout and other blends. Total intake can add up across products. The meta-analyses read show that many studies used combinations, so a result for one ingredient may not apply to a blend. 7 13 1
| Body | Action | Date |
|---|---|---|
| MedlinePlus (US National Library of Medicine) (United States) | The encyclopedia page lists arginine as a nonessential and a conditionally essential amino acid (usually not essential, except in illness and stress). It does not set an upper limit or give supplement advice. MedlinePlus's own herbs and supplements list has no arginine or citrulline entry, and says the Natural Medicines database content has been unavailable since 2025-07-29. source | 2025-01-21 |
When to get medical help
- Chest pain, shortness of breath, a very fast, slow or uneven heartbeat, or fainting after taking arginine: call emergency services.
- Dizziness or fainting, especially if you also take blood pressure or heart medicines: sit or lie down and get medical help if it does not pass.
- Muscle weakness, tingling or palpitations in someone with kidney or liver disease who took arginine (possible high potassium): get urgent medical help.
- Someone with an inherited urea cycle disorder who becomes confused, very sleepy, vomits repeatedly or has seizures: this can be high ammonia, get emergency help.
Stop using the product and contact a clinician or emergency service. In the US, Poison Control is 1-800-222-1222.
General information only, not medical advice. Ask a clinician or pharmacist before use, especially with medicines, in pregnancy or with a health condition. See the Natural Remedy Safety guide.
Frequently asked questions
What are arginine and citrulline?
What is the difference between arginine and citrulline?
What foods have arginine?
By USDA data, pumpkin seeds, walnuts, chicken, beef, salmon, lentils, chickpeas and eggs all contain it. An ounce of pumpkin seeds has about 1.5 g. USDA gives no citrulline value for watermelon.
Does arginine lower blood pressure?
Does citrulline or watermelon lower blood pressure?
A 2025 meta-analysis of 15 trials in older adults found small drops with citrulline pills and watermelon pooled together. It did not separate citrulline alone.
Does citrulline help exercise?
Does arginine help erectile dysfunction?
Is arginine safe after a heart attack?
The trial's authors said it should not be recommended. In a trial of 153 people after a first heart attack, 6 people on arginine died versus none on placebo, Ask a cardiologist before taking it.
Does arginine interact with medicines?
Possibly. It lowers blood pressure in trials, so it could add to blood pressure or nitrate medicines, though that was not tested. A small meta-analysis found no clear rise in side effects with PDE5 drugs. A 1978 case report linked intravenous arginine to dangerous potassium in two very sick people. Ask a pharmacist.
Can arginine or citrulline help with diabetes?
A meta-analysis of 12 trials found no significant effect of arginine on fasting blood sugar, insulin, HbA1c or insulin resistance.
Are they safe in pregnancy, breastfeeding and for children?
Trials in pregnancy were for pre-eclampsia, run within pregnancy care, with low-certainty results. No safety data were read for breastfeeding or for children. Ask a doctor or midwife before any amino acid supplement.
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Editorial transparency
- Written by
- AlternativeMed editorial team. Research compiled with AI assistance, then checked against the sources listed.
- Medical review
- None. This page has not been reviewed by a physician or pharmacist.
- First published
- 2026-10-26
- Last substantive update
- 2026-10-26
- How we research
- We started from our existing amino acid summary, read MedlinePlus pages, re-checked food values in saved USDA FoodData Central data, and re-read PubMed abstracts for reviews, trials and a case report. Only abstracts were read for studies. The NIH Office of Dietary Supplements site was blocked and is marked unread.
- How we rate evidence
- See "How we rate evidence" in the Evidence tab.
- Independence
- No product is promoted on this page. No affiliate links are shown. Trials of supplements may have manufacturer links not stated in abstracts; one tolerance review was run under a nonprofit amino acid council whose funders are not named.
Sources 22
Each source was opened and checked. Where we read only the abstract, it says so. The small numbers in the text point here.
- Aguiar AF, Casonatto J. Effects of Citrulline Malate Supplementation on Muscle Strength in Resistance-Trained Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.. J Diet Suppl. 2022. PMID 34176406. DOI 10.1080/19390211.2021.1939473. (abstract)
- Bushinsky DA, Gennari FJ. Life-threatening hyperkalemia induced by arginine.. Ann Intern Med. 1978. PMID 717931. DOI 10.7326/0003-4819-89-5-632. (abstract)
- Davani-Davari D, Karimzadeh I, Sagheb MM, et al.. The Renal Safety of L-Carnitine, L-Arginine, and Glutamine in Athletes and Bodybuilders.. J Ren Nutr. 2019. PMID 30341034. DOI 10.1053/j.jrn.2018.08.014. (abstract)
- Elango R. Tolerable Upper Intake Level for Individual Amino Acids in Humans: A Narrative Review of Recent Clinical Studies.. Adv Nutr. 2023. PMID 37062432. DOI 10.1016/j.advnut.2023.04.004. (abstract)
- Harnden CS, Agu J, Gascoyne T. Effects of citrulline on endurance performance in young healthy adults: a systematic review and meta-analysis.. J Int Soc Sports Nutr. 2023. PMID 37155582. DOI 10.1080/15502783.2023.2209056. (abstract)
- Karimi E, Hatami E, Ghavami A, et al.. Effects of L-arginine supplementation on biomarkers of glycemic control: a systematic review and meta-analysis of randomised clinical trials.. Arch Physiol Biochem. 2023. PMID 33426939. DOI 10.1080/13813455.2020.1863991. (abstract)
- Luo P, Chen J, Liu K, 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. PMID 40789388. DOI 10.1016/j.clnesp.2025.07.1130. (abstract)
- Makama M, McDougall ARA, Cao J, et al.. L-Arginine and L-Citrulline for Prevention and Treatment of Pre-Eclampsia: A Systematic Review and Meta-Analysis.. BJOG. 2025. PMID 39800868. DOI 10.1111/1471-0528.18070. (abstract)
- Morris CR, Hamilton-Reeves J, Martindale RG, et al.. Acquired Amino Acid Deficiencies: A Focus on Arginine and Glutamine.. Nutr Clin Pract. 2017. PMID 28388380. DOI 10.1177/0884533617691250. (abstract)
- Schulman SP, Becker LC, Kass DA, et al.. L-arginine therapy in acute myocardial infarction: the Vascular Interaction With Age in Myocardial Infarction (VINTAGE MI) randomized clinical trial.. JAMA. 2006. PMID 16391217. DOI 10.1001/jama.295.1.58. (abstract)
- Shi Y, Liu Y, Zhou Z, 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. PMID 42520885. DOI 10.1016/j.niox.2026.07.004. (abstract)
- Shiraseb F, Asbaghi O, Bagheri R, et al.. Effect of l-Arginine Supplementation on Blood Pressure in Adults: A Systematic Review and Dose-Response Meta-analysis of Randomized Clinical Trials.. Adv Nutr. 2022. PMID 34967840. DOI 10.1093/advances/nmab155. (abstract)
- Tian Y, Zhou Q, Li W, et al.. Efficacy of L-arginine and Pycnogenol in the treatment of male erectile dysfunction: a systematic review and meta-analysis.. Front Endocrinol. 2023. PMID 37908749. DOI 10.3389/fendo.2023.1211720. (abstract)
- Valenzuela PL, Morales JS, Emanuele E, et al.. Supplements with purported effects on muscle mass and strength.. Eur J Nutr. 2019. PMID 30604177. DOI 10.1007/s00394-018-1882-z. (abstract)
- Viribay A, Fernandez-Landa J, Castaneda-Babarro A, et al.. Effects of Citrulline Supplementation on Different Aerobic Exercise Performance Outcomes: A Systematic Review and Meta-Analysis.. Nutrients. 2022. PMID 36079738. DOI 10.3390/nu14173479. (abstract)
- Xu Z, Liu C, Liu S, et al.. Comparison of efficacy and safety of daily oral L-arginine and PDE5Is alone or combination in treating erectile dysfunction: A systematic review and meta-analysis of randomised controlled trials.. Andrologia. 2021. PMID 33587304. DOI 10.1111/and.14007. (abstract)
- . MedlinePlus Medical Encyclopedia: Amino acids (review date 2025-01-21). . . (full-text)
- . MedlinePlus Genetics: Arginase deficiency (last updated 2024-02-13). . . (full-text)
- . MedlinePlus Genetics: Citrullinemia (last updated 2017-05-01). . . (full-text)
- . MedlinePlus: Herbs and Supplements A-Z list. . . (full-text)
- . NIH Office of Dietary Supplements fact sheets. . . (not-read)
- . USDA FoodData Central, SR Legacy (April 2018 release): arginine in foods. . . (full-text)
Where to buy
Check the label first. Whatever you buy, look for these:
- The amount of the active ingredient per serving, not just the front-label claim
- A third-party testing mark (USP, NSF or ConsumerLab)
- Other ingredients and allergens
- Ask a pharmacist about interactions with your medicines
Talk to a pharmacist or doctor before you start any supplement, especially if you take medicines. See the Safety tab for interactions.
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