Arginine supplement benefit and side effects, nitric oxide increase, dosage and review of research studies by Ray Sahelian, M.D.
Supplement Information, capsules and powder, is it safe? What are the short term and long term benefits? Does it help with heart disease or erectile dysfunction? Does it benefit those with high blood pressure?
September 15 2014

L-Arginine is an amino acid involved in ammonia detoxification, hormone secretion, and the immune system. It is is also well known as a precursor to nitric oxide, a key component of endothelial-derived relaxing factor. The endothelium is the lining inside blood vessels and arginine supplements help make more nitric oxide which helps to relax and dilate blood vessels. There have been claims that this amino acid is useful in hypertension, preeclampsia, intermittent claudication, and erectile dysfunction. It has been studied for its role in athletic performance, burns and trauma, diabetes and syndrome X, male and female infertility, and interstitial cystitis. What does the research say about its benefits for various medical conditions?
   Even though arginine supplements have been claimed to be useful for some of the conditions listed above, it would be premature to be overly excited. Much research needs to be done before we can be more confident about its role in health and disease. However, thus far, it appears to have a role to play in conditions involving blood vessel dilation. Whether this dilation is short lived or continues for an adequate period is still being evaluated. Blood levels of arginine after supplementation usually return back to normal after a few hours of ingestion.

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Serving size 1 capsule
L Arginine hcl 750 mg per capsule

Usage and dosage, how much to take: Take 1 to 10 arginine supplement capsules daily, preferably on an empty stomach, or as directed by your qualified health consultant. As with most nutrients I recommend taking breaks from use. It appears to be safe to take for extended periods as long as the dose is less than 3 grams a day. If your dose is 1 to 4 g, the capsule is a good option. If you plan to take more than 4 grams, then the powder is more a more efficient method.

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As a rule, Passion Rx is potent by itself and there is little need to take any other supplements the same day. L arginine is quite benign, and we don't foresee any additional side effects if this amino acid is added.

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Erectile dysfunction studies, is it effective as an impotence treatment? Can it cure erectile dysfunction?
One of the more popular supplements for sexual dysfunction is L-arginine amino acid. It is a versatile amino acid in animal cells, serving as a precursor for the making not only of proteins but also of nitric oxide, urea, glutamate, and creatine. What makes it interesting is that it can be metabolized to nitric oxide (NO). NO is the most powerful chemical known to dilate and engorge blood vessels in the penis and clitoris. In my opinion, I am not impressed with the effectiveness of this amino acid in turns of impotence or ED treatment. There are many other aphrodisiac herbs that are much more potent and effective. What does the research say about its role in erectile dysfunction or impotence treatment?

Efficacy and safety of l-arginine aspartate 8 g combined with 200 mg of adenosine monophosphate with placebo alone for intermittent treatment of mild-to-moderate erectile dysfunction (ED) were compared. ED patients demonstrated significant improvements in erectile function but no changes in sexual desire and orgasms. A randomized, double-blind, crossover, placebo-controlled comparative clinical trial of arginine aspartate plus adenosine monophosphate for the intermittent treatment of male erectile dysfunction. Andrology 2013.

A Low dose, at 500 mg three times a day, was not found to be effective for erectile dysfunction since it takes at least several grams to have a noticeable effect on nitric oxide production.

A double-blind, placebo-controlled study of 50 men with erectile dysfunction tested a dose of 5 grams per day for six weeks. About a third of the participants who received l arginine showed improvement, and that improvement was greater than the 10% improvement seen in the placebo group.

A small trial found some improvement with a combination treatment providing a daily dose of 2,500 mg of l arginine, as well as ginseng, ginkgo, and damiana. In a four-week, double-blind study, 77 women with decreased libido were given either the combination product or a placebo. Those taking the arginine blend showed statistically greater improvement, reporting increased sexual desire in 71% of participants given the treatment. In the placebo group, 42% reported an increased libido. Other improvements included relative satisfaction with sex life and heightened clitoral sensation. No significant side effects were seen in either group. However, we don't know if the arginine had anything to do with the results.

A study done at the University of Texas at Austin examined arginine, combined with yohimbine, on sexual arousal in postmenopausal women. Twenty-four women participated in three sessions in which sexual responses to erotic stimuli were measured following treatment with either arginine glutamate 6 grams plus yohimbine 6 mg, yohimbine alone 6 mg, or a placebo. Compared to placebo, the combined oral administration substantially increased vaginal pulse amplitude responses to the erotic film after one hour. It is well known that yohimbine, alone, has a significant effect on sexuality and whether arginine was a factor is not known.

Mechanism of action, how it works
The most likely explanation for its mild effectiveness is its conversion into nitric oxide. As discussed in Natural Sex Boosters book, nitric oxide is converted into cGMP, which becomes the secondary messenger that causes smooth muscle relaxation, resulting in blood vessel dilation, and more blood going into the genital organs, which leads to erections. However, nitric oxide is quickly metabolized and any potential l arginine benefit could be short lived. L It is a semi-essential amino acid synthesized by the body from ornithine. This amino acid supports protein synthesis as it is involved in the transport and storage of nitrogen. Among many functions, it is used by the body to produce creatine. 

Benefits and uses
There is some supporting evidence that l arginine offers benefits in reducing angina and lowering blood pressure, along with post heart transplant patients. Research indicates supplementation reduces pulmonary resistance and blood pressure. Supplementation improves renal function in patients with chronic heart failure. Polish researchers have found that supplements increases exercise tolerance in stable coronary artery disease patients. Oral L-arginine improves endothelial function in older healthy individuals.

Body building, muscle growth
I'm much more impressed with creatine monhydrate and protein powders than l arginine for body building.

Cancer or tumors
I don't see any reason why use would cause or prevent a cancer or tumor.

Exercise and athletic performance
Researchers at the University of Exeter in England say taking a dietary supplement containing L-arginine amino acid to enhance the production of nitric oxide in the body can significantly boost stamina during high-intensity exercise. The study, published in the 2010 Journal of Applied Physiology, suggests taking the supplement can allow athletes to exercise up to 20 percent longer.

Growth hormone release
Some claim that the use of this amino acid supplement in large dosages increases human growth hormone levels. It so, the effects are minor and a better option is to exercise daily. Exercise is a much more potent and consistent way to increase growth hormone levels.

Heart attack
It would seem prudent to not use this amino acid product the first few months after a heart attack. However, at least one or two additional studies are needed to determine whether the results of this study regarding the influence of l arginine supplements and heart attack were coincidence or whether it does have a negative impact on heart health in those who have had a recent heart attack.

L-arginine therapy in acute myocardial infarction: the Vascular Interaction With Age in Myocardial Infarction (VINTAGE MI) randomized clinical trial.
JAMA. 2006..
A total of 153 patients following a first ST-segment elevation myocardial infarction were enrolled; 77 patients were 60 years or older. Patients were randomly assigned to receive L-arginine (goal dose of 3 g 3 times a day) or matching placebo for 6 months. There was no significant change from baseline to 6 months in the vascular stiffness measurements or left ventricular ejection fraction in either of the 2 groups, including those 60 years or older and the entire study group. However, 6 participants (8%) in the L-arginine group died during the 6-month study period vs none in the placebo group. L-arginine, when added to standard postinfarction therapies, does not improve vascular stiffness measurements or ejection fraction and may be associated with higher postinfarction mortality.

Benefit for heart failure and heart disease
L-arginine supplements may improve the physical fitness of heart failure patients by enhancing their endurance to exercise. Dr. Stephane Doutreleau and colleagues from Institut de Physiologie, Strasbourg, France, examined the potential benefits of 6 weeks of L-arginine supplements on endurance exercise in 10 patients with chronic stable heart failure. Patients who took it experienced a significant decrease in their average heart rate throughout exercise and the recovery period. There were no significant changes in blood pressure and respiratory parameters. The current study supports a prior study in which a group of heart failure patients were shown to benefit from a combination of exercise and L-arginine supplements. In that study, the combination appeared to help correct the abnormal functioning of blood vessels seen in chronic heart failure. International Journal of Sports Medicine July 2006.

Heart transplant patients
Dr. Stephane Doutreleau, from Nouvel Hopital Civil, Strasbourg, France, first compared clinical, echocardiographic, and exercise characteristics in 22 heart recipients (all at least 6 months post-transplant) and 11 healthy control subjects. At baseline the heart recipients had a lower exercise capacity than controls. Dr. Stephane Doutreleau then randomized the transplant patients to receive a 6-week treatment of either placebo or L-arginine. At 6 weeks, the amino acid group had improvements in quality of life and exercise capacity, whereas the placebo group had no change from baseline. With L-arginine, the mean distance on the 6-minute walk test increasedm. During bicycle exercise testing, the ventilator threshold during the incremental test was delayed by 1 minute. Patients in the L-arginine group also had lower resting and maximal heart rates after treatment. There was an improvement in quality of life. American J Clinical Nutrition, 2010.

Hypertension, high blood pressure
I need to see more studies to determine how effective this supplement is for reducing high blood pressure, what the right dosage would be, and how long the effects last after taking such a supplement. Some early studies show promise but I would like to see additional papers.

Evaluation of the antihypertensive effect of L-arginine supplementation in patients with mild hypertension assessed with ambulatory blood pressure monitoring.
Med Sci Monit. 2010.
The study was completed by 54 participants. Ambulatory blood pressure monitoring was used to allot patients to either a healthy control group (19 subjects) or the hypertensive treatment group (35 patients). Later the patients were randomized to either L-arginine (2 or 4 g three times daily or placebo. Blood pressure (both systolic and diastolic) showed statistically significant lowering after 4 weeks of supplementation only in the subgroup of patients treated with 12 g daily, with a stronger hypotensive effect observed during the day. The present findings demonstrate a strong association between supplementation and blood pressure reduction.

Benefit in gestational hypertension
L-arginine supplementation in patients with gestational hypertension: a pilot study.
Hypertens Pregnancy. 2007.
Patients with gestational hypertension and proteinuria and those without proteinuria were randomized in a double-blind design to receive either L arginine (20 grams / 500 mL intravenously daily, for 5 days followed by 4 grams /day orally for 2 weeks) or placebo. Compared with baseline, both systolic and diastolic blood pressure 6 days after treatment were significantly reduced in the treatment group but not in the placebo group.

Homocysteine
Oral L arginine supplement improves hemodynamic responses to stress and reduces plasma homocysteine in hypercholesterolemic men.
J Nutr. 2005.
We tested whether oral l-arginine (12 grams per d for 3 weeks) affected hemodynamics, glucose, insulin, or C-reactive protein in 16 middle-age men with high cholesterol. This study is the first to describe a hemodynamic mechanism for the hypotensive effect of oral l arginine and the first to show substantial reductions in homocysteine with oral administration.

Nitric oxide production studies and research
Arginine is a precursor of nitric oxide, which causes blood vessel relaxation. Although there is some evidence that suggests that arginine supplements may be useful in the treatment of medical conditions that are improved by vasodilation, such as angina, atherosclerosis, coronary artery disease, erectile dysfunction, heart failure, intermittent claudication / peripheral vascular disease, and vascular headache, more proof is needed. Arginine also stimulates protein synthesis and has been studied for wound healing, bodybuilding, enhancement of sperm production (spermatogenesis), and prevention of wasting in people with critical illness.

The influence of two different doses of L arginine oral supplementation on nitric oxide NO concentration and total antioxidant status in atherosclerotic patients.
Med Sci Monit. 2004.
The purpose of this study was to assess the effect of two different doses, 6 grams and 12 grams, in 28-day arginine oral supplementation on nitric oxide NO concentration and total antioxidant status in patients with atherosclerotic peripheral arterial disease. Oral supplementation of L arginine for 28 days leads to substantial increases in nitric oxide and antioxidant levels in the blood of patients with atherosclerotic peripheral arterial disease.

If I take an arginine supplement, how long does it take to convert into nitric oxide and how long does the nitric oxide stay in the body?
    These are excellent questions and at this time I don't know the precise answers but will search for such research. Nitiric oxide stays in the blood stream for brief periods.

Nocturnal leg cramps
Email - I used to have nocturnal leg cramps several times a week. I have not had any at all since I started taking L-arginine capsules.

Peripheral artery disease not helpful
L-arginine supplementation in peripheral arterial disease: no benefit and possible harm. Circulation. 2007.

Preeclampsia not helpful
Dietary supplementation with L-arginine or placebo in women with pre-eclampsia.
Staff AC.. Departments of Obstetrics and Gynecology, Ulleval University Hospital, Oslo, Norway.
The women received orally 12 grams of L arginine or placebo daily for up to 5 days. Supplementation did not reduce mean diastolic blood pressure after 2 days of treatment compared with placebo in pre-eclamptic patients with gestational length varying from 28 to 36 weeks.

Sexual enhancement benefit
There are many potent herbs that have sexual enhancement properties. Arginine is not on my top ten list of aphrodisiac supplements and I don't think it provides significant erection enhancement except perhaps in very high amounts.

Dosage
L Arginine is available most often as 750 to 1,000 mg capsules and in powder form. The dosage of depends on the condition being treated. In some cases, a dosage of more than 5 grams a day may be required.

Different forms and types
I came across a web site that said: Arginine Ornithine Lysine is an obvious choice to promote health and wellbeing at all stages of adult life. What's the scoop?
   I have not come across any studies that indicate arginine ornithine lysine together help promote health.

Cream
I am interested in information regarding arginine as a cream. Is it as effective as the capsules? Where do I buy it?
    I have not seen studies with the cream application. I seriously doubt enough would get absorbed for it to be effective.

I recently happened across a company, Stategic Science, Inc., promoting the topical application of arginine cream (and their transdermal delivery system) to restore hair growth - essentially by improving blood flow to the hair follicles in the scalp. Also, I read recently that "Kevis" is actually the number one selling hair loss treatment in the world, followed closely by Rogaine minoxidil in north America. From what I've read, the active ingredient in Kevis is hyaluronic acid which purports to restore depleted collagen around hair follicles, while minoxidil dilates blood vessels. Since Kevis and Rogaine were originally patented and sold by UpJohn. As an alternative to the minoxidil / finasteride approach, I was wondering if topical arginine, perhaps in conjunction with hyaluronic acid, would be worth considering.
   Since we have not seen studies with arginine cream and hair growth, and the same for hyaluronic acid, we can't say whether these two nutrients in the form of a cream would be effective to restore hair loss.

History, discovery
L arginine was first isolated in 1886. In 1932, it was found to be required for the generation of urea, which is necessary for the removal of toxic ammonia from the body. In 1939 it was also shown to be required for the synthesis of creatine, the muscle builder.

Deficiency
Symptoms of arginine deficiency include poor wound healing, hair loss, skin rash, constipation, and fatty liver. This is a semi-essential amino acid, because although it is normally synthesized in sufficient amounts by the body, supplementation is sometimes required (for example, due to inborn errors of urea synthesis, protein malnutrition, excessive lysine intake, burns, peritoneal dialysis, and rapid growth).

What are some foods high in arginine?
All foods that have protein contain this amino acid.

L Arginine side effects, safety, risk, danger, toxicity, overdose
I have not come across any significant l arginine side effects up to now. It is possible that one adverse effect with  high dosage is nausea. Other possible side effects on very high dosages are digestive disturbances. I have personally taken more than 10 grams at one time at least on three different occasions without any significant adverse effects. But, it is not clear whether it causes negative reaction if used in high dosages daily for many months or years.
   It is unlikely that dosages of less than 3 grams a day would lead to any untoward effects.

I have followed your career since my wife and I heard you at a book review at the La Quinta Hotel several years ago. I was taking l arginine 6 grams per day over several months and came down with rosacea, which cleared up when I stopped taking it and with standard treatment by a dermatologist. I have read stories by body builders of their faces getting "rough" when taking large doses and wonder if they have undiagnosed rosacea. Keep up the good work.
   Thanks, this is the first I have heard of rosacea as an adverse reaction.

Ornithine, arginine, amino acids, and human growth hormone release

Certain amino acids can stimulate the release of growth hormone when infused intravenously or administered orally. Some individuals ingest amino acids before strength training workouts thinking that this enhances exercise-induced growth hormone release thereby promoting greater gains in muscle mass and strength. Although IV arginine administration consistently leads to increased circulating growth hormone concentration, oral arginine doses that are great enough to induce significant growth hormone release are likely to cause stomach discomfort and diarrhea. During exercise intensity is a major determinant of growth hormone release. Up to now studies have not consistently found that pre-exercise oral amino acid supplementation to enhance growth hormone release. In addition, no major studies have found that oral supplementation with amino acids such as arginine or ornithine before strength training increases muscle mass and strength to a greater extent than strength training alone.

Metabolism by the kidneys
The kidney plays a major role in arginine metabolism in 3 principal ways: arginine synthesis, creatine synthesis, and arginine reabsorption. Arginine is made in the kidney from citrulline produced by the intestine. The renal enzymes of synthesis, argininosuccinate synthetase and argininosuccinate lyase, occur in the cells of the proximal tubule. The rate of synthesis depends on citrulline delivery and does not appear to be regulated by dietary arginine availability. Renal synthesis in humans produces approximately 2 grams per day, which may be compared to an intake, from a Western diet, of approximately 4 to 5 grams a day.

Use by women
Is l arginine for a woman appropriate? What is the correct dosage? Also, is it a vitamin?
   I need to see more studies to determine whether a woman would need to take such a supplement. It is not a vitamin but an amino acid.

Testimonial
Q. Let me first say that your site is a welcome source of information and discussion. I'm a 29 year old relatively healthy male with no other conditions. Arginine in moderate to high daily doses (up to 10 grams) I've seen the following gains: greatly improved sleep, increase in reduction of body fat, faster wound healing, faster growth or hair and nails, improved skin quality and hair quality, slightly improved recovery time from strenuous workouts, ahem... sexual enhancement. I otherwise take rice protein powder, a multivitamin, and a multimineral as my daily regimen or stack. As a recovery supplement, I have gotten better results from glutamine and whey protein. However, I haven't taken another supplement where I've seen this number of beneficial results in about 4 months of supplementation without real world side effects other than its horrible taste. Should I be worrying about damaging my heart with this supplement?
    A. There are few studies regarding the long term use of supplements. It is difficult to predict the consequences in any one individual taking high dosage supplements for prolonged periods, but, as a general rule, it is a good idea to take breaks from the use of supplements and certain medications, to minimize any potential adverse effects.

Various misspellings include arganine and argenine