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L-arginine, the Conditionally Essential Amino Acid

L-arginine, which we’ll just refer to as arginine, is a conditionally essential amino acid. This means that some people sometimes need it, and most people usually don’t.

Adding to the confusion, purveyors of arginine supplements typically try to persuade the healthy people who need the smallest amounts of arginine to take the most, and the people who really could benefit from high-dose arginine not to take enough. Let’s begin to sort through the claims about arginine to get the truth of the matter by exploring the idea of a “conditionally essential” amino acid.

Why Some People Need Arginine Sometimes, and in Varying Doses

The human body makes proteins out of building blocks called amino acids. The synthesis of proteins requires having the right amino acids in the right order. Having just one amino acid out of thousands in a protein chain can change the function of the entire molecule. Every amino acid is essential for its position in a chain of amino acids that makes up a protein, but not every amino acid has to be obtained from the diet.

L-Arginine Structure

The human body cannot ever make isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. These essential amino acids always have to come from food or supplements.

The human body sometimes can make the amino acids alanine, asparagine, aspartate (or aspartic acid), citrulline, cysteine, glutamate (or glutamic acid), glutamine, glycine, histidine, ornithine, proline, serine, and tyrosine from the essential amino acids. These are the “non-essential” amino acids. If the essentials are not provided, however, the body cannot make the non-essentials, so, to add to the confusion in the nomenclature, nutritionists often refer to these amino acids as “conditionally essential.”

If the adult human body gets more of the essential amino acids than it needs in its dietary forms, it can convert them into the other amino acids it needs. If there is a shortage of these amino acids, it may dissolve white blood cells or muscle tissue, breaking them down into needed components for critical repairs. And if there is an excess of an amino acid, the body can convert it into sugar.

And what about arginine? The body sometimes can make arginine, and sometimes it can’t. Infants can’t make arginine. Elderly people often don’t make arginine. When a healthy adult body is not increasing muscle mass or repairing damaged tissues, it can make all the arginine it needs from essential amino acids. But if the body is building muscle or rebuilding injured tissues, a small amount of supplemental arginine can accelerate the process.

And there are cardiovascular conditions for which high doses of supplemental arginine practically work wonders. But how much is enough?

How Arginine Does the Body Need?

A typical Western diet provides from 3 to 6 grams of arginine per day, which is more than a healthy body needs for maintenance, and less than a healthy body sometimes needs for growth or repair. But the amount of arginine provided by the diet is not a whole lot less than the body needs, even for growth and repair.

Researchers Douglas Paddon-Jones, Elisabet Borsheim, and Robert R. Wolfe at the Shriner’s Hospital for Children in Galveston, Texas in the USA report research finding that it only takes 1 gram (1,000 mg) of supplemental arginine with 1 gram (1,000 mg) of supplemental ornithine daily to enhance muscle building in athletes on a high-intensity strength-building program. (If you are concerned about the nuances of absorption among the various arginine pyroglutamate, arginine alpha-ketoglutarate, arginine ethyl ester, and arginine hydrochloride supplements, just take 2 pills instead of 1, and you’re covered.) If you are working out to build muscle, it only takes 1,000 mg of arginine a day, with 1,000 mg of ornithine a day, to enhance muscle growth.

Ornithine is included with arginine because the body tends to convert arginine into ornithine and citrulline, reducing the amount of arginine available to the muscles.

Arginine supplements are often recommended for athletes who have broken bones. Professor of nutrition and Canadian hockey team trainer Dr. John Berardi has recommended 7 grams of arginine, 7 grams of glutamine, and 1,500 mg of HMB (beta-hydroxy-beta-methybutyric acid) to support recovery from broken bones and torn ligaments.

On the other hand, it takes a lot more arginine in an athlete’s stack to get any “NO2” effects. First a word about “NO2” effects. There actually aren’t any. Arginine helps the body make NO, nitric oxide, a beneficial free radical, not NO2, nitrogen dioxide, a gas. NO helps arteries dilate for easier circulation of blood, lower blood pressure, and in both sexes, greater sexual response.

Nobel laureate Dr. Joseph Ignarro (you may see references in the literature to him as Louis J. Ignarro) reports that in his patients, it takes about 9 grams of supplemental arginine every day to be able to detect a change in the arginine concentration of blood plasma. Since NO is made by cells in the lining of blood vessels, you have to get a change in the arginine concentration of blood plasma to make a difference in the production of NO.

For arginine to act as a secretagogue for the release of growth hormone, the required dosages are even higher. Growth hormone, as you probably know:

  • Stimulates muscle growth by increasing protein synthesis in the sarcomere that powers the muscle (rather than by combining with water, as creatine does),
  • Stimulates breakdown of fat in fat cells,
  • Helps the bones take up the minerals they need for new bone,
  • Stimulates the immune system,
  • Encourages the release of sugar by the liver during exercise,
  • Protects the islets of Langerhans in the pancreas, which are the cells that make hormones that regulate blood sugar levels and appetite, and
  • Stimulates the growth of all internal organs except the brain.

Technically, high arginine levels inhibit the release of somatostatin, which ordinarily limits the release of growth hormone. However, one study found that arginine supplementation could increase the nighttime release of growth hormone in men aged 20 to 35 by 60%.

There were two significant downsides to that study. One was that men aged 20 to 35 typically don’t need additional growth hormone. Men and women aged 50 and up might. The amount of arginine needed to enhance the production of growth hormone in young, healthy males was 250 mg per kg of body weight, or 1000 for every 4 pounds. A person who weighs 100 kg (220 pounds) would need to take at least twenty-five 1,000 mg capsules of arginine every night, about an hour before bed, to have any expectation of increased hormone production.

Can you get, for instance, 25,000 mg of arginine a day from your diet?

Food as a Source of Arginine

Arginine is found in “high-protein” foods. Shellfish and soy protein are especially rich in arginine. This amino acid is also found in beef, nuts, sesame seeds, peanuts, almonds, Brazil nuts, chicken (especially canned chicken, which has about 30% more arginine than fresh), halibut, and mayonnaise. There is more arginine in light meat than in dark meat. There is more arginine in animal foods than in plant foods, with the exception of Brazil nuts.

Nutritional science knows of no better source of arginine than sea lion livers, a 200-calorie serving providing nearly 5 grams of arginine. Sea lion livers, of course, are not a practical food outside of eastern Siberia and western Alaska. They’re usually eaten raw, by the way.

A 200-calorie serving of soy protein isolate, which is a lot to add to a shake, provides about 4 grams of arginine. A 200-calorie serving of steamed shrimp also provides about 4 grams of arginine. That’s the equivalent of about 200 grams/half a pound of steamed shrimp. A pound (approximately 450 grams) of ready-to-cook turkey breast yields about 3 grams of arginine.

Or, looking at it a different way, it would be reasonable to assume that you can get the arginine you need for supporting increased growth hormone levels by cooking and eating 8-1/3 pounds (about 3500 grams) of turkey breast every day. The problem with this is that only about 90% of arginine is digested from food, which means you would need 9 pounds (a little under 4 kilos), and only about 50% of the arginine that is digested is accepted by the liver, which means you would need to start with 18 pounds (a little under 9 kilos) of turkey just to get the arginine. Prefer a vegan approach? Then eat eight 10-oz packages of spinach.

There are no diets that include eating a whole turkey or eight packages of spinach every day. To get more than about 6 grams of arginine a day, it’s essential to supplement. But it really doesn’t make a lot of difference in which kind of arginine you take.

Varieties of Arginine Supplements

The arginine used to make the familiar, 1000 mg capsules is arginine hydrochloride, also known as arginine HCl. For most applications, this is the kind of arginine I’d recommend. There are theoretical advantages to other arginine formulas:

  • Arginine pyroglutamate is often described as an “excellent growth hormone releaser.” It is the form of arginine used in tests of arginine supplementation and growth hormone release, but since we really don’t know what the right dosage of arginine is for supporting somatostatin restriction and growth hormone enhancement in people who are actually interested in increasing growth hormone, it’s an exaggeration to claim arginine pyroglutamate is better or worse for increasing growth hormone. We simply don’t know.
  • Arginine alpha-ketoglutarate has been tested as an ergogenic (muscle-building) aid at Baylor University in Texas in the USA, twice. You have to look at the research findings very carefully to see what the benefit is. Maximal strength (for a one-time push) was increased in exercisers who took 12 grams of a popular arginine alpha-ketoglutarate supplement for eight weeks. There were no other observable benefits from taking arginine alpha-ketoglutarate-and this was four times the manufacturer’s recommended dose. (Perhaps taking less is what was needed?) Researchers at Baylor didn’t find any “general health” benefits from taking arginine alpha-ketoglutarate, at least in the short term.
  • Arginine ethyl ester is the form of arginine used in sports powders such as Axis Labs NE2, Ultimate Horse Power, Live Long Nutrition, and Xero Limits. It is extremely bitter, and you have to cover up the taste with sugar, artificial sweetener, or juice. That’s a major downside if you are working out to lose weight while maintaining or growing muscle. There is, in fact, a pharmacological benefit in arginine ethyl ester. A lot more than 50% of the product is actually absorbed into your bloodstream. But if you are taking in a lot more calories with the sweeteners you need to keep from spewing the product out, you aren’t doing yourself a lot of good. Dr. Ignarro’s studies suggest that you would need about 20 grams of these products to be sure of getting 9-12 grams of arginine into your system for the “NO boost,” the manufacturers claim. That’s 5 heaping tablespoons. And that’s a lot of bitterness you have to cover up.

If Arginine Isn’t All that Great for Bodybuilders, Is It Any Use At All?

I think that most bodybuilders max out on the benefits of taking arginine at two capsules of arginine HCl. If you really want to boost growth hormone, try an eat-stop-eat program. Fasting increases growth hormone release (to protect muscle tissue) many times more than taking arginine. Or if you take citrulline to prevent soreness, taking one or two capsules of arginine may extend citrulline’s effects. But the people who really can benefit tremendously from arginine supplements are people who have peripheral arterial disease. ( More about L-Arginine and Bodybuilding. )

What is peripheral arterial disease, also known as PAD?

If you have PAD, you probably first notice something is wrong by looking at your toes. The skin on your toes may peel as if they had been sunburned, even when they haven’t been out in the sun. You might develop “blood blisters” under your toenails or on the sides of your feet. Eventually, the tissue heals over. The skin on your legs may look “rusty” and then dry out and crack. And at some point, it may hurt a lot, to run or even to walk.

PAD occurs when the linings of the arteries don’t make enough NO (nitric oxide). Strictly speaking, the arteries don’t convert arginine into NO. They use arginine to make an enzyme called endothelial NO synthase, which enables them to release NO. The release of nitric oxide doesn’t just “relax” the arteries. It also prevents platelets from sticking together. This prevents clotting and “no-flow” situations, but it also prevents high blood viscosity and “low-flow” situations.

Increased production of NO keeps white blood cells from adhering to the linings of blood vessels. When white blood cells do not attach themselves to the linings of blood vessels, they do not transform cholesterol into hardened, artery-clogging plaques. The provision of arginine keeps the cells lining arteries from undergoing apoptosis, a series of changes sometimes called “cellular suicide.” And arginine also helps normalize the pH of the blood, reduces the production of harmful free radicals of oxygen, and acts as an Angiotensin-converting enzyme inhibitor (like the blood pressure medication lisinopril, only without the side effect of dry cough).

Who is most likely to benefit from taking supplemental arginine to treat or prevent PAD?

  • People who have high cholesterol levels tend to have low arginine levels because of reactions that convert arginine to an inert form, asymmetric dimethylarginine.
  • People who smoke experience tissue damage from the release of free radicals of oxygen, which are quenched by enzymes the body makes with arginine.
  • People who have prediabetes may reverse insulin resistance by taking arginine. The arginine helps open up blood vessels in both fat and muscles so more cells can respond to insulin and lower blood sugar levels more quickly. The pancreas does not produce as much insulin, and it becomes easier to lose weight.
  • People who have full-blown type 2 diabetes typically have lower levels of arginine in the bloodstream. Taking supplemental arginine lowers blood pressure and protects the kidneys.

How much arginine should people who have PAD or who are at risk of PAD take? Dr. Joseph Ignarro, a UCLA scientist who won his Nobel Prize for his work on the role of arginine in vascular health, says that it takes at least 9 grams a day to make a difference in bloodstream arginine concentrations. Lower amounts of arginine may help muscle growth, but they won’t change NO synthesis. Up to 30 grams of arginine a day may make a difference, although this amount can cause stomach upset.

If you have PAD, and you see improvement in your legs, you may be inclined to tolerate a little stomach upset. However, some people should not take arginine supplements at all.

  • If you are on Plavix, Coumadin, Trental, or another prescription blood thinner, don’t take supplemental arginine. The combination of the blood thinning drug and arginine supplements may be greater than the prothrombin (PT) time test your doctor orders to track your progress with the blood thinning drug can detect.
  • If you have herpes, HIV, or any other chronic viral infection, avoid arginine supplements. They may activate viral growth.
  • If you are being treated for a solid, cancerous tumor, discontinue arginine supplements until after you are in remission. There is no evidence that arginine causes cancer, but there is a possibility it may help certain kinds of cancers grow, just as it helps muscles grow.

What kind of arginine should you take for cardiovascular conditions? I am skeptical of the benefits of arginine powders. They taste bad, and they don’t really make any difference with muscle growth. If you simply cannot take 20 capsules a day, then I would use 20 grams of arginine ethyl ester in beverages as the manufacturer suggests on the label. It won’t taste good, but it will be easy to swallow.

Otherwise, I recommend arginine HCl (arginine hydrochloride) capsules. They are inexpensive. They are easy to store, and they work. You don’t need to spend a lot of extra money to get a high dose of potentially beneficial arginine. Always work with your doctor on any supplement program, discussing all medical concerns with your physician in person before you start.

Frequently Asked Questions:

Q. I have been taking a supplement that contains 500 mg of arginine, pycnogenol, and hawthorn berries for heart support. Is this a good combination?

A. It would depend on the amount of pycnogenol. That is not enough arginine to make a difference. Sometimes manufacturers add ingredients that have no direct health benefit for marketing or patent protection. It could be that the arginine is just “there” to distinguish the product from a competitor or to prevent a claim of patent infringement.

Q. Will arginine help enlarge my penis?

A. I have no direct information on this. It is possible that erections might be firmer.

Selected References:

Adams M. R., McCredie R., Jessup W., Robinson J., Sullivan D., Celermajer D. S. Oral L-arginine improves endothelium-dependent dilatation and reduces monocyte adhesion to endothelial cells in young men with coronary artery disease. Atherosclerosis 1997;129:261-269.

Agullo L., Garcia-Dorado D., Inserte J., Paniagua A., Pyrhonen P., Llevadot J., Soler-Soler J. L-Arginine limits myocardial cell death secondary to hypoxia-reoxygenation by a cGMP-dependent mechanism. Am. J. Physiol. 1999;276:H1574-H1580.

Blum A., Hathaway L., Mincemoyer R., Schenke W. H., Kirby M., Csako G., Waclawiw M. A., Panza J. A., Cannon R. O. Oral L-arginine in patients with coronary artery disease on medical management. Circulation 2000;101:2160-2164.

Bocchi E. A., de Moraes A. V., Esteves A., Bacal F., Auler J. O., Carmona M. J., Bellotti G., Ramires A. F. L-Arginine reduces heart rate and improves hemodynamics in severe congestive heart failure. Clin. Cardiol. 2000;23:205-210.

Boger R., Bode-Boger S. M., Thiele W., Alexander K., Frolich J. C. Biochemical evidence for impaired nitric oxide synthesis in patients with peripheral arterial occlusive disease. Circulation 1998;95:2068-2074.

Chauhan A., More R. S., Mullins P. A., Taylor G., Petch M. C., Schofield P. M. Aging-associated endothelial dysfunction in humans is reversed by L-arginine. J. Am. Coll. Cardiol. 1996;28:1796-1804.

Hambrecht R., Hilbrich L., Erbs S., Gielen S., Fiehn E., Schoene N., Schiler G. Correction of endothelial dysfunction in chronic heart failure: additional effects of exercise training and oral L-arginine supplementation. J. Am. Coll. Cardiol. 2000;35:706-713.

Higashi Y., Oshima T., Ozono R., Matsuura H., Kambe M., Kajiyama G. Effect of L-arginine infusion on systemic and renal hemodynamics in hypertensive patients. Am. J. Hypertens. 1999;12:8-15.

Kidd G. A., Dobrucki L. W., Brovkovych V., Bohr D. F., Malinski T. Nitric oxide deficiency contributes to large cerebral infarct size. Hypertension 2000;35:1111-1118.

Lerman A., Burnett J. C., Higano S. T., McKinley L. J., Holmes D. R., Jr Long-term L-arginine supplementation improves small-vessel coronary endothelial function in humans. Circulation 1998;97:2123-2128.

Marfella R., Nappo F., De Angelis L., Paolisso G., Tagliamonte M. R., Giugliano D. Hemodynamic effects of acute hyperglycemia in type 2 diabetic patients. Diabetes Care 2000;23:658-663.

Maxwell A. J., Anderson B. E., Cooke J. P. Nutritional therapy for peripheral arterial disease: a double-blind, placebo-controlled, randomized trial of HeartBar. Vasc. Med. 2000;5:11-19.

Ozcelikay A. T., Tay A., Guner S., Tasyaran V., Yildizoglu-Ari N., Dincer U. D., Altan V. M. Reversal effects of L-arginine treatment on blood pressure and vascular responsiveness of streptozotocin-diabetic rats. Pharmacol. Res. 2000;41:201-209.

Pieper G. M. Review of alteration in endothelial nitric oxide production in diabetes. Hypertension 1998;31:1047-1060.

Rector T. S., Bank A. J., Mullen K. A., Tschmumperlin L. K., Sih R., Pillai K., Kubo S. H. Randomized, double-blind, placebo-controlled study of supplemental oral L-arginine in patients with heart failure. Circulation 1996;93:2135-2141.

Shankar R. R., Wu Y. G., Shen H. Q., Zhu J. S., Baron A. D. Mice with gene disruption of both endothelial and neuronal nitric oxide synthase exhibit insulin resistance. Diabetes 2000;49:684-687.

Susic D., Francischetti A., Frohlich E. D. Prolonged L-arginine on cardiovascular mass and myocardial hemodynamics and collagen in aged spontaneously hypertensive rats and normal rats. Hypertension 1999;33:451-455.

Wascher T. C., Graier W. F., Dittrich P., Hussain M. A., Bahadori B., Wallner S., Toplak H. Effects of low-dose L-arginine on insulin-mediated vasodilatation and insulin sensitivity. Eur. J. Clin. Investig. 1997;27:690-695.

Watanabe G., Tomiyama H., Doba N. Effects of oral administration of L-arginine on renal function in patients with heart failure. J. Hypertens. 2000;18:229-234.