Arginine

Arginine is one of the 20 amino acids that proteins are made from. The body also makes it, but not always in enough quantity. That makes it a conditionally essential (conditionally indispensable) amino acid.

The National Academies (NASEM, 2005), the WHO, FAO and UN University (2007) and EFSA (2012) all place it outside the nine essential amino acids. Instead it is in a group that can become indispensable under some conditions. Examples are premature babies and children with certain inherited urea cycle defects. NASEM calls it dispensable in healthy people because it is synthesized in adequate amounts.

The “L-” in L-arginine names the form that proteins are made from, and it is the form in food and in supplements.

Beyond building protein, the body turns arginine into nitric oxide, a gas that relaxes blood vessels. It also makes creatine from it, and urea, which carries ammonia out of the body. The kidneys make about 2 g of arginine a day, and a Western diet supplies another 4 to 5 g. Seeds, nuts, legumes, meat and fish are rich in it, as the rankings below show.

The thing most readers do not know is how far the supplement’s story has moved from its biochemistry. Arginine is the raw material for nitric oxide, whose discovery as a body signal won a Nobel Prize in 1998. That made it a popular supplement for blood pressure and circulation.

The trials are more sobering. After a heart attack, 6 people given about 9 g a day died against none on placebo, and the trial closed early. In artery disease, 3 g a day for 6 months did not help. The gains that were found are small: meta-analyses put the effect on blood pressure at about 4 to 6 mmHg (the unit for blood pressure).

Health benefits of arginine

• ★★Lower blood pressure with arginine supplementsIn 22 small, short trials, arginine supplements lowered blood pressure: the top number by 6.4 mm Hg, the bottom by 2.6 mm Hg. A review of 5 trials with 24-hour monitors found the top number 4.2 mm Hg lower.
• ★★Less gut disease in premature babiesArginine given by mouth or vein cut the risk of necrotizing enterocolitis, a serious gut disease, to 0.38 times (3 trials, 285 babies). The authors say three small trials are not enough for a recommendation.
• ★★Better erectile function in some menA review of 10 trials found the odds of improvement 3.37 times as high, though some trials mixed arginine with other substances. A trial of arginine alone (6 g daily) moved 74% of men with poor blood flow to a milder category; only 24% reached normal scores.
• ★★No benefit after a heart attackIn 153 people after a heart attack, about 9 g a day for 6 months did not change artery stiffness or heart pumping. Six people on arginine died against none on placebo, and the trial closed enrollment.
• ★★No help for leg pain from poor circulationIn 133 people with leg pain from poor circulation, 3 g a day for 6 months did not improve nitric oxide measures. Walking distance improved 11.5% on arginine and 28.3% on placebo.

Foods high in arginine

Seeds and nuts lead the USDA (US Department of Agriculture) ranking per 100 g. Pumpkin seeds come first with 5.35 g, then hemp seeds (4.55 g) and peanuts (3.09 g).

Per serving, soybeans come first with 2.22 g in a cup. Shrimp (1.91 g in 3 oz) and chicken breast (1.72 g in 4 oz) follow. Per 100 kcal, lean seafood and poultry rank highest: shrimp 1.89 g, then cod 1.3 g and tuna 1.28 g. The ranking below has the full lists.

Arginine has no official daily need, so we compare servings with the typical intake. NASEM reports a mean of about 4.2 g a day from food and supplements in a US survey from 1988 to 1994. By our arithmetic, one cup of soybeans (2.22 g) is 53% of that. 4 oz of chicken breast (1.72 g) is 41%, and a cup of lentils (1.38 g) 33%.

Unlike lysine in grains, arginine is not known as the weak link of any food group. NASEM puts the arginine in typical mixed dietary protein at about 5.4 g per 100 g of protein.

The WHO’s table of adult amino acid requirements lists only the nine essential amino acids and has no arginine row. So there is no arginine score for foods like the lysine scores on the lysine page. Animal and plant protein can both supply it.

How arginine works

Most of the biochemistry below is well established. But it comes from reviews, cell and animal work and small human studies, not from trials of extra arginine.

Four ideas cover it. The body makes arginine in a relay between gut and kidneys, and turns it into nitric oxide. The body also feeds it into the urea cycle and creatine, and takes it up on carriers it shares with other amino acids. Here is each one, and what has been seen in people.

The gut and kidneys make it

Arginine is made from glutamine, glutamate and proline through what researchers call the intestinal-renal axis, according to a 2009 review. A review of kidney metabolism puts it more simply: the gut makes citrulline, and the kidney turns it into arginine.

In humans, kidney synthesis produces about 2 g a day, against 4 to 5 g a day from a Western diet. It follows how much citrulline arrives rather than how much arginine is eaten, and in rats citrulline supply limits the rate. NASEM describes the same pathway from ornithine, which the body can make from proline and possibly from glutamate.

The relay is slow to start in premature babies. A review proposes that their gut makes too little citrulline and arginine, which would explain their low blood arginine.

It is the raw material for nitric oxide

In 1988, Palmer, Ashton and Moncada showed that cultured artery cells make nitric oxide (NO) from L-arginine. D-arginine and close look-alikes did not work. NO is a gas signal.

When the Nobel Assembly honored the field in 1998, it explained how NO works. NO made by the inner layer of the arteries spreads to the muscle cells beneath and turns off their contraction. That widens the artery, which controls blood pressure and how blood is shared out. The prize went to Furchgott, Ignarro and Murad for showing that NO is a signal molecule in the cardiovascular system.

There is a puzzle, called the arginine paradox. Blood arginine is already about 25 to 30 times the level that the purified enzyme needs, yet extra arginine improves artery function in some studies.

The leading explanation is asymmetric dimethylarginine (ADMA), a natural blocker of the enzyme. ADMA is raised in high cholesterol, atherosclerosis, high blood pressure, kidney failure and heart failure. Extra arginine may outcompete it. Reviews suggest the people who gain most are those with a high ADMA or a low arginine-to-ADMA ratio.

That fits the meta-analysis above in which only people with low baseline artery function gained. But the peripheral artery disease trial found that long-term arginine did not raise nitric oxide measures.

It feeds the urea cycle and makes creatine

NASEM says arginine is needed to make other amino acids, polyamines and creatine, and to clear ammonia through the urea cycle. Reviews list its main exits as four enzymes. Arginase makes ornithine and urea; then come nitric oxide synthase, arginine:glycine amidinotransferase (the first step of creatine) and arginine decarboxylase, which makes agmatine.

Ornithine can go on to polyamines, proline and glutamate. The kidney makes the first creatine intermediate, guanidinoacetate. The body loses 1 to 2 g of creatine as creatinine a day. That has to be replaced from food and from its own production.

Cats show how much the urea cycle matters. In 1978, near-adult cats given one meal of amino acids without arginine developed ammonia poisoning within 2 hours. One died 4.5 hours after eating 8 g of the diet.

Because ornithine also prevented the problem, the authors concluded that the cat cannot make ornithine. People can, but NASEM notes that in children with inherited defects of two urea cycle enzymes, arginine becomes indispensable.

How much gets through

Taken by mouth, arginine is partly broken down on the way into the blood. In 10 volunteers, the absolute bioavailability (the share that reaches the blood) of a 10 g oral dose was about 20%. A study that compared it with citrulline blames arginase in the gut wall.

The carrier that takes arginine up in the kidney tubules also carries lysine, ornithine and cystine. Defects of these carriers cause cystinuria and lysinuric protein intolerance, with arginine lost in the urine. The kidney salvages about 3 g of arginine a day this way.

At high doses the gut reacts. A review explains that arginine at high levels makes the gut secrete water through nitric oxide, which fits the diarrhea seen with large single doses. The chart puts the doses in perspective.

What has been seen in people

The clearest human findings are about blood pressure and a few special groups. Meta-analyses of small, short trials find drops of about 4 to 6 mmHg. A Cochrane review of 3 small trials found less necrotizing enterocolitis in premature babies.

Beyond that the picture is mixed. After a heart attack, and in people with poor leg circulation, long courses of arginine did not help. The heart attack trial also raised safety concerns.

In prediabetes, 6.4 g a day did not cut new diabetes. Erectile dysfunction, sickle cell crises, pressure ulcers and exercise each show positive and null results, and several positive trials used blends.

Small studies of growth hormone fit the same pattern. In 8 men, 5 and 9 g of oral arginine raised growth hormone, while 13 g caused considerable stomach distress with no larger rise. In 14 men, 0.075 and 0.15 g per kg raised blood arginine but not growth hormone, insulin or nitric oxide products at rest. Most of these trials are among the study cards above.

How much arginine do you need?

No daily amount of arginine is officially recommended. The body makes it, so healthy people are not expected to need a set amount from food.

NASEM (2005) and the WHO, FAO and UN University (2007) give requirement values for the nine essential amino acids only. The WHO’s summary table of adult requirements has no arginine row. Neither the FDA nor the EU sets a Daily Value for arginine. EFSA’s 2012 opinion sets values for protein only and derives none for amino acids, which are eaten as protein.

For scale, NASEM reports a mean arginine intake of about 4.2 g a day from food and supplements. That figure comes from the US survey of 1988 to 1994.

At the 99th percentile it was 10.1 g a day, in men aged 51 to 70. NASEM puts arginine in typical mixed dietary protein at about 5.4 g per 100 g of protein. The kidneys add about 2 g a day, according to a review of kidney metabolism.

The body can fall short in special conditions. NASEM says arginine becomes indispensable, with daily supplementation required, in children with inherited defects of two urea cycle enzymes, argininosuccinic acid synthetase and argininosuccinase. EFSA names premature newborns as another example of a group that can run short of it.

Arginine deficiency: signs and who is at risk

Official sources describe risk groups, not a checklist of signs of low dietary arginine in healthy adults. Premature babies are the best-described group.

A review says severe low blood arginine (hypoargininemia) is a nutritional problem in preterm infants. It is linked to high blood ammonia and to heart, lung, brain and gut problems. The review proposes that the premature gut cannot yet make enough citrulline and arginine.

Inherited urea cycle disorders are the other group. In citrullinemia type I, caused by a fault in the enzyme argininosuccinate synthase, newborns can develop high ammonia, lethargy and vomiting. Daily treatment includes protein restriction, ammonia-clearing drugs and arginine supplementation, according to GeneReviews.

Arginase 1 deficiency is the opposite problem: the enzyme that breaks arginine down is missing. Treatment aims to normalize plasma arginine with protein restriction, an arginine-free essential amino acid formula and, in some patients, an enzyme drug. These conditions need a specialist.

Rare carrier defects, cystinuria and lysinuric protein intolerance, make the kidneys lose arginine, lysine and ornithine in the urine.

Low arginine also shows up in illness. In a trial in young people aged 3 to 21 hospitalized for sickle cell pain crises, 79% had low arginine on arrival. Their mean was 50 µmol/L, and lower arginine availability went with a longer time to recovery in the placebo group.

Forms of arginine: absorption and effects

Arginine supplements differ in what comes with the arginine. Most trials used L-arginine as the free base or as a salt, the hydrochloride or the aspartate. A few used arginine alpha-ketoglutarate, a complex with silicon and inositol, or a blend.

The weight of the salt is not the weight of the arginine. In one trial, 30 g of the hydrochloride held 24.8 g of free arginine and 30 g of the aspartate held 17 g. Compare the label’s milligrams of arginine, not of the salt.

Whatever the form, the body takes up only part of an oral dose, about 20% of a 10 g dose in one study. The only head-to-head we found is a three-arm trial of the hydrochloride, the aspartate and placebo. It compared each salt with placebo and not with the other, so we found no trial showing that one salt is better than another.

For popular claims about muscle “pumps”, special complexes or time-release forms, we found no trial showing an advantage over plain arginine. Citrulline raised blood arginine more than arginine itself in one small study. But we did not review citrulline trials for health outcomes, so we cannot say which works better.

Form	What it is	What studies show	Source
L-arginine (free base)	The free amino acid, all arginine by weight (molecular weight 174.20).	The reference for the forms below. In 10 volunteers the absolute bioavailability of a 10 g oral dose was about 20%, with a peak at 1 hour. NASEM reports 30 g of free base a day for 3 days in breast cancer patients, in the Park trial above.	1, 3, 4
L-arginine hydrochloride	Salt with hydrochloric acid. Arginine is about 83% of its weight (174.20 of 210.66, our arithmetic), which matches the 24.8 g of arginine in 30 g reported in the wound trial.	Used at 30 g a day for 2 weeks in the wound trial, where NASEM reports mild hyperchloremic acidosis and bloating, mild loss of appetite or diarrhea in 6 of 12 people, against 3 of 12 on the aspartate and 1 of 12 on placebo. Also the form in the sickle cell trial (100 mg per kg three times a day) and in 15 people with heart failure (5.6 to 12.6 g a day), who walked farther on arginine than on placebo.	2, 4, 5, 7, 8
L-arginine aspartate	Salt with aspartic acid. 30 g held 17 g of free arginine in the wound trial (57%, our arithmetic).	Raised wound collagen and lymphocyte responses at 30 g a day in healthy young and elderly volunteers. NASEM reports weight gain, stomach upset and sleepiness at 5 or 10 g of free arginine for 80 days, and no adverse effects in 30 elderly adults at 17 g for 14 days. With 200 mg of adenosine monophosphate, 8 g taken before sex improved erection scores in 26 men in a crossover trial, which is a blend.	4, 5, 6, 9
Arginine alpha-ketoglutarate	Arginine with alpha-ketoglutarate, sold for muscle “pumps”. The arginine share is not stated in the abstracts.	Two acute trials found no benefit: 3,000 mg did not change bench press or leg press in 8 trained and 8 untrained men, and 3,700 mg doses before exercise did not improve endurance, and chin-ups fell (23.75 against 25.58).	10, 11
L-citrulline (related compound)	A different amino acid that is readily absorbed and at least partly converted to arginine in the body.	Raised blood arginine more than arginine itself in 20 volunteers, and no treatment improved flow-mediated dilation over baseline. The only citrulline trial in the pre-eclampsia meta-analysis had 36 women and found no effect. We did not review citrulline trials for health outcomes.	12, 13
Arginine blends	Arginine sold or tested with other ingredients.	Arginine with antioxidant vitamins in a food bar cut pre-eclampsia in women at high risk (absolute risk reduction 0.17 against placebo), while vitamins alone did not. A formula with zinc and antioxidants helped pressure ulcers (200 people). Arginine with Pycnogenol improved erectile function in 3 studies (184 men). Arginine with liposomal vitamin C improved walking in 46 adults with long COVID in a single-blind trial. None can credit its result to arginine alone.	14, 15, 16, 17
Arginine silicate inositol	A complex of arginine with silicon and inositol. One preparation was reported as 49.5% arginine, 8.2% silicon and 25% inositol by weight.	Rat studies of wound healing, bone healing and arthritis. In people we found two small crossover trials of single doses (1.5 g in 19 young adults, 1,600 mg in 26 gamers) that reported better memory scores or reaction times than placebo. One author declares industry ties. Both compared it with placebo, not with plain arginine.	18, 19, 20, 21, 22
D-arginine	The mirror-image form. Proteins and nitric oxide production use the L-form.	In the 1988 cell study, D-arginine did not boost nitric oxide release as L-arginine did. We found no human trial of D-arginine.	23
Arginine in food protein	Arginine released when protein is digested, about 5.4 g per 100 g of mixed dietary protein (NASEM).	The typical intake is about 4.2 g a day. We found no study that compares the blood response to arginine in food with the same amount taken as a supplement.	4

Here are the head-to-head and form-specific studies, five in all, all with limited evidence.

Is arginine safe? Supplements, dose and interactions

Arginine from food is not a concern. NASEM says there is no evidence that amino acids from usual or even high protein intakes from food present any risk. It focused on supplements.

For arginine, NASEM could identify neither a dose with no observed harm nor a lowest dose with observed harm in healthy people. So it set no tolerable upper intake level, the most a person can safely take each day. It adds that arginine supplements are not advisable other than in children with certain inherited urea cycle defects. It cites a small breast cancer study that it calls unconfirmed.

We found no EFSA upper level for arginine, and EFSA’s 2012 opinion says the data are not sufficient to set one for protein. We found no authorized EU health claim for arginine in Regulation (EU) No 432/2012. For scale, NASEM puts mean US intake from food and supplements at 4.2 g a day. The 99th percentile for men aged 51 to 70 is 10.1 g.

• Doses and stomach effects. A review of side effects found that single doses of 3 to 6 g rarely caused trouble. Most side effects came with single doses above 9 g in adults, often as part of about 30 g a day. They were mainly nausea and diarrhea, and they disappeared when the dose was split. NASEM reports nausea in 2 and diarrhea in 3 of 21 people given 30 g of arginine hydrochloride a day for 7 days. It also reports weight gain, stomach upset and sleepiness with 5 or 10 g of free arginine as aspartate for 80 days. In 8 men, a single 13 g dose caused considerable stomach distress.
• Heart attack, circulation and cancer. After a heart attack, the VINTAGE MI trial closed enrollment after 6 deaths on arginine and none on placebo. Its authors say arginine should not be recommended in that setting. In peripheral artery disease, 3 g a day for 6 months did not help, and walking improved less than on placebo. In a small randomized study of breast cancer patients, arginine raised tumor protein synthesis, which NASEM calls an unconfirmed finding. If you have heart disease or cancer, ask a doctor before using arginine.
• Medicines and conditions. Arginine lowered blood pressure in trials, by about 4 to 6 mmHg. So tell a doctor if you take blood pressure medicine, nitrates or erectile dysfunction drugs. We found one trial of a combination. Adding 3 g of arginine a day to sildenafil for 8 weeks gave slightly better scores, 19.8 against 18.5, and more gastritis. The sildenafil dose was 50 mg every other day. We found no study of arginine with nitrates. An infusion of arginine hydrochloride caused life-threatening high potassium in 2 patients with severe liver disease and moderate kidney failure. Both had recently taken spironolactone. NASEM calls such reports acute toxicity that says little about chronic intake. But they are a reason to ask a doctor first if you have kidney or liver disease. In tissue culture, herpes simplex virus replication was suppressed when arginine was missing, and lysine worked against arginine’s growth-promoting action. We found no trial in people (see the lysine page).
• Pregnancy, children and inherited disorders. Arginine was given to pregnant women in 20 randomized trials with 2,028 women, which the meta-analysis above rates as low-certainty evidence. We found no safety limit for pregnancy. NASEM reports that 17 infants with high ammonia had no adverse effects, under medical care. They were given 175 to 350 mg per kg a day for 6 to 8 weeks. In arginase 1 deficiency, GeneReviews describes treatment with an arginine-free amino acid formula, so these patients follow a specialist’s plan, not supplements. Ask a doctor first if you are pregnant or have kidney, liver or metabolic disease.

How to get more arginine

• Best foods. A cup of soybeans gives 2.22 g, 4 oz of chicken breast 1.72 g and a cup of lentils 1.38 g. By our arithmetic, that is 53%, 41% and 33% of the 4.2 g a day the average US adult takes in.
• Seeds and nuts. Per 100 g, pumpkin seeds hold 5.35 g, hemp seeds 4.55 g and peanuts 3.09 g, and 3 tbsp of hemp seeds give 1.37 g.
• Eat enough protein, and skip the pill unless a doctor suggests one. Arginine makes up about 5.4 g of every 100 g of mixed dietary protein, and the kidneys add about 2 g a day. So a varied diet covers it, and no health body names a daily need. The trial results for blood pressure, erectile dysfunction and exercise are mixed, and some are negative.

History of arginine

The German chemist Ernst Schulze and his assistant Ernst Steiger first isolated arginine in 1886, from yellow lupin seedlings. Its role in animals showed up in 1978. That year, Morris and Rogers fed near-adult cats a single meal without arginine and found ammonia poisoning within 2 hours.

The big change came in 1988, when Palmer, Ashton and Moncada showed that artery cells make nitric oxide from L-arginine. Furchgott, Ignarro and Murad received the 1998 Nobel Prize in Physiology or Medicine for discovering nitric oxide as a signal molecule in the cardiovascular system.

The supplement trials followed. In 1996 a crossover trial in 15 people with heart failure reported better walking distance on 5.6 to 12.6 g of arginine hydrochloride a day.

Larger trials then gave sobering results. VINTAGE MI in 2006, after a heart attack, closed enrollment after 6 deaths on arginine and none on placebo. The NO-PAIN trial in 2007 found no benefit and possible harm in artery disease.

Frequently asked questions about arginine

Is arginine an essential amino acid?

Not in the strict sense. NASEM (2005) lists nine essential amino acids and puts arginine among the conditionally indispensable ones. That means a dietary source is needed when the body’s own production cannot meet the need. It calls arginine dispensable in healthy people because it is synthesized in adequate amounts, but says children with certain urea cycle defects need it daily. The WHO (2007) and EFSA (2012) also list it as conditionally indispensable, and EFSA names premature newborns as an example.

Does arginine lower blood pressure?

A little, in small and short trials. A 2022 meta-analysis of 22 trials found oral arginine lowered systolic pressure by 6.4 mmHg and diastolic by 2.6 mmHg. There was no clear change above 9 g a day. A 2026 meta-analysis of 5 trials with 24-hour monitors found drops of 4.2 and 3.0 mmHg. Neither shows fewer heart attacks. After a heart attack, a trial aiming for about 9 g a day found no benefit and 6 deaths on arginine against none on placebo.

How much arginine can you take a day?

No official upper limit exists. NASEM could not set one because it found no safe or lowest-harm level in healthy people. It does not advise supplements except for children with certain inherited defects. Trials mostly used 1.5 to 9 g a day. A review found that single doses of 3 to 6 g rarely caused trouble. Most side effects, mainly nausea and diarrhea, came with single doses above 9 g. Ask a doctor first if you have heart disease, kidney or liver disease, or take blood pressure medicine.

Which foods are highest in arginine?

Per 100 g, pumpkin seeds lead our USDA ranking with 5.35 g. Hemp seeds (4.55 g), peanuts (3.09 g), sesame seeds (2.63 g) and almonds (2.47 g) follow. Per serving, soybeans give 2.22 g in a cup, shrimp 1.91 g in 3 oz and chicken breast 1.72 g in 4 oz. The average US adult takes in about 4.2 g a day, according to NASEM.

Is citrulline better than arginine?

It raised blood arginine more in one study. In 20 healthy volunteers, citrulline raised plasma arginine more than arginine itself. Taking 3 g twice a day lifted the arginine to ADMA ratio from 186 to 278. Only about 20% of a 10 g oral dose of arginine reached the blood in another study. No treatment improved flow-mediated dilation in the citrulline study. We did not review citrulline trials for health outcomes, so we cannot say which works better.

Does arginine help erectile dysfunction?

Maybe a little in mild to moderate cases, but the results are mixed. A meta-analysis of 10 trials in 540 men found higher odds of improvement (odds ratio 3.37) at 1,500 to 5,000 mg a day. Some of those trials combined arginine with other ingredients. A trial of 6 g a day for 3 months improved scores in men with vascular erectile dysfunction, but only 24% reached normal scores. Ask a doctor before combining arginine with erectile dysfunction drugs.

What is arginine vasopressin deficiency?

It is a hormone problem, not an amino acid problem. In 2022 a group of endocrine societies proposed the name arginine vasopressin deficiency (AVP-D) for central diabetes insipidus. In that condition, too little of the hormone vasopressin leads to large volumes of dilute urine. The kidney form is called arginine vasopressin resistance (AVP-R). No source we found links either condition to the arginine you eat or take as a supplement.

Does arginine make herpes worse?

It might in a dish, but we found no trial in people. In a 1981 tissue-culture study, herpes simplex virus replication was suppressed when arginine was missing. Lysine worked against arginine’s growth-promoting action. The authors suggested that people prone to herpetic lesions avoid excess arginine. We found no trial of arginine intake or restriction in people; the trials of lysine for cold sores are on the lysine page.