What is arginine as a dietary supplement?

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Natural substance used as a dietary supplement for specific health benefits.
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Overview

Arginine is an amino acid found in many foods, including dairy products, meats, poultry, fish, nuts, and chocolate. It plays a role in several important mechanisms in the body, including cell division, wound healing, removal of ammonia from the body, immunity to illness, and the secretion of important hormones.

The body also uses arginine to make nitric oxide (NO), a substance that relaxes blood vessels and also exerts numerous other effects in the body. Based on this, arginine has been proposed as a treatment for various cardiovascular diseases, including congestive heart failure and intermittent claudication, as well as impotence, female sexual dysfunction, interstitial cystitis, and many other conditions. Arginine’s potential effects on immunity have also created an interest in using it as part of an immune “cocktail” given to severely ill hospitalized persons and also for preventing colds.

Requirements and Sources

Normally, the body either gets enough arginine from food or manufactures what it needs from other widely available nutrients. Certain stresses, such as severe burns, infections, and injuries, can deplete the body’s supply of arginine. For this reason, arginine (combined with other nutrients) is used in a hospital setting to help enhance recovery from severe injury or illness.

Therapeutic Dosages

A typical supplemental dosage of arginine is 2 to 8 grams (g) per day. For congestive heart failure, higher dosages up to 15 g have been used in trials. However, one should not try to self-treat congestive heart failure.

Therapeutic Uses

Small double-blind, placebo-controlled studies suggest that arginine might be helpful for the treatment of several seemingly unrelated conditions that are all linked by arginine’s effects on NO: congestive heart failure, intermittent claudication, angina, impotence, and sexual dysfunction in women. The first three conditions in this list are life-threatening. Persons with angina, congestive heart failure, or intermittent claudication should not attempt to self-treat with arginine except under a physician’s supervision.

Arginine has been proposed for use after a heart attack to aid recovery. In one study, arginine did not cause harm and showed potential modest benefit. However, in another study, arginine failed to prove helpful for treatment of people who had just had a heart attack, and it possibly increased the post-heart-attack death rate.

A small, double-blind, placebo-controlled study suggests that use of arginine (700 milligrams [mg] four times daily) may support transdermal nitroglycerin therapy for angina. Ordinarily, the drug nitroglycerin becomes less effective over time, as the body develops a tolerance to it. However, arginine supplements appear to help prevent the development of tolerance.

The results of one controlled (but not blinded) study in women suggest that arginine might help standard fertility therapy for women (specifically, in vitro fertilization) work better. However, studies have not found any benefit in male infertility.

Weak evidence suggests that arginine might improve insulin action in people with type 2 diabetes. Nutritional mixtures containing arginine have shown promise for enhancing recovery from major surgery, injury, or illness, perhaps by enhancing immunity. Highly preliminary evidence suggests that arginine might be worth investigating as a treatment for pulmonary hypertension in people with sickle cell disease.

Conflicting results have been seen in preliminary double-blind studies of arginine for preeclampsia. Preliminary double-blind studies have failed to find arginine helpful for asthma, cystic fibrosis, interstitial cystitis, kidney failure, osteoporosis, or Raynaud’s phenomenon. One study found that an arginine-rich food bar did not help relax arteries or thin the blood in people with high cholesterol.

A study of 133 people with intermittent claudication (pain in the legs caused by atherosclerosis) failed to find arginine helpful; in fact, arginine was less effective than placebo, suggesting that it actually increases symptoms to some extent. Two earlier studies had reported benefit, but they were small and poorly designed and reported.

One preliminary, double-blind study suggests that arginine supplementation might help prevent colds. Also, arginine has been proposed for preventing altitude sickness, but the one reported study found harmful effects (increase in headache) rather than beneficial ones.

Scientific Evidence

The first three conditions in this section are life-threatening. Persons with angina, congestive heart failure, or intermittent claudication should not self-treat with arginine except under a physician’s supervision.

Congestive heart failure. Three small double-blind, placebo-controlled studies enrolling a total of about seventy persons with congestive heart failure found that oral arginine at a dose of 5 to 15 g daily could significantly improve symptoms and objective measurements of heart function.

Intermittent claudication. People with advanced hardening of the arteries, or atherosclerosis, often have difficulty walking because of a lack of blood flow to the legs, a condition known as intermittent claudication. Pain may develop after walking less than half a block.

In a double-blind study of forty-one persons, two weeks of treatment with a high dose of arginine improved walking distance by 66 percent; no benefits were seen in the placebo group or in a low-dose arginine group. Good results also were seen in another study, although its convoluted design makes interpreting the results somewhat difficult.

Angina. A double-blind study of twenty-five persons with angina pectoris found that treatment with arginine at a dose of 6 g per day improved exercise tolerance, but not objective measurements of heart function. A double-blind, placebo-controlled crossover trial of thirty-six persons with heart disease found that the use of arginine (along with antioxidant vitamins and minerals) at a daily dose of 6.6 g reduced symptoms of angina.

Impotence. The substance NO plays a role in the development of an erection. Drugs such as Viagra increase the body’s sensitivity to the natural rise in NO that occurs with sexual stimulation. A simpler approach might be to raise levels of this substance, and one way to accomplish this involves use of the amino acid L-arginine. Oral arginine supplements may increase NO levels in the penis and elsewhere. Based on this, L-arginine has been advertised as “natural Viagra.” However, there is little evidence that it works. Drugs based on raising NO levels in the penis have not worked for pharmaceutical developers; the body seems simply to adjust to the higher levels and maintain the same level of response.

Nonetheless, some small studies have found possible evidence of benefit. In a double-blind trial, fifty men with erectile dysfunction received 5 g of either arginine or a placebo per day for six weeks. More men in the treated group experienced improvement in sexual performance than in the placebo group.

A double-blind crossover study of thirty-two men found no benefit with 1,500 mg of arginine daily for seventeen days. However, the lower dose of arginine and the shorter course of treatment may explain the discrepancy between these two studies.

Arginine also has been evaluated in combination with the drug yohimbine (as opposed to the herb yohimbe). A double-blind, placebo-controlled trial of forty-five men found that one-time use of this combination therapy one hour or two before intercourse improved erectile function, especially in those with only moderate erectile dysfunction scores. Arginine and yohimbine were both taken at a dose of 6 g. Note, however, that one should not use the drug yohimbine (or the herb yohimbe) except under physician supervision, because it presents a number of safety risks.

One study reportedly found that arginine plus oligomeric proanthocyanidins (OPCs) can improve male sexual function, but because the study lacked a placebo group, it did not find anything. A small, unpublished, double-blind study listed on a manufacturer’s Web site reported benefits with a proprietary combination of arginine; the herbs ginseng, ginkgo, and damiana; and vitamins and minerals.

Sexual dysfunction in women. Some postmenopausal women have difficulty experiencing sexual arousal. One small double-blind study of yohimbine combined with arginine found an increase in measured physical arousal among twenty-three women with this condition. However, the women themselves did not report any noticeable subjective effects, suggesting that the effect was slight. In addition, only the combination of yohimbine and arginine produced results; neither substance was effective when taken on its own. Slight benefits were also seen in preliminary double-blind, placebo-controlled trials that evaluated a combination therapy containing arginine; the herbs ginseng, ginkgo, and damiana; and vitamins and minerals.

Interstitial cystitis. Interstitial cystitis is a condition in which a person feels like he or she has symptoms of a bladder infection, but no infection is present. Medical treatment for this condition is less than satisfactory.

A three-month, double-blind trial of fifty-three persons with interstitial cystitis found only weak indications that arginine might improve symptoms. Several participants dropped out of the study; when this was properly taken into account using a statistical method called ITT analysis, no benefit could be proven.

Colds. A two-month, double-blind study involving forty children with a history of frequent colds concluded that arginine seemed to provide some protection against respiratory infections. Of the children who were given arginine, fifteen stayed well during the sixty days of the study. By contrast, only five of the children who took placebo stayed well, a significant difference.

Nutritional support in hospitalized persons. Several nutritional products that contain arginine and other substances have been tried in hospital settings to enhance recovery following major surgery, illness, or injury. These mixtures are delivered enterally, through a tube into the stomach. A review of fifteen studies, about one-half of them double-blind and involving 1,557 persons, found that such products can reduce episodes of infection, time on ventilator machines, and length of stay in the hospital. However, because of the many nutrients contained in these so-called immunonutrient mixtures, it is not clear whether arginine deserves the credit.

Safety Issues

There is good evidence that arginine is safe and well tolerated at levels up to 20 g per day, although minor gastrointestinal upset can occur. However, there are some potential safety issues regarding high-dose arginine. These cautions are based on findings from animal studies and hospital experiences of intravenous administration.

For example, arginine may stimulate the body’s production of gastrin, a hormone that increases stomach acid. For this reason, there are concerns that arginine could be harmful for people who have ulcers or take drugs that are hard on the stomach. In addition, a double-blind trial found that arginine (30 g/day) may increase the risk of esophageal reflux (heartburn) by relaxing the sphincter at the bottom of the esophagus.

Arginine might also alter potassium levels in the body, especially in people with severe liver disease. This is a potential concern for persons who take drugs that also alter potassium balance (such as potassium-sparing diuretics and angiotensin-converting enzyme, or ACE, inhibitors) and for those with severe kidney disease. Persons in any of these categories should not use high-dose arginine except under physician supervision.

Evidence that arginine can improve insulin sensitivity raises theoretical concerns that if a patient has diabetes and takes arginine, his or her blood sugar could fall too low. However, one study suggests that arginine is safe for use by people with stable type 2 diabetes.

The amino acid lysine has been advocated for use in oral or genital herpes. According to the theory behind this recommendation, it is important to simultaneously restrict arginine intake. If true, this would tend to suggest that arginine supplements would be harmful for people with a tendency to develop herpes. However, there is no meaningful evidence to support this hypothesis.

Maximum safe doses in pregnant or nursing women, young children, and those with severe liver or kidney disease have not been established.

Important Interactions

Persons taking lysine to treat herpes should note that arginine use might counteract the potential benefit of the lysine. For persons using drugs that are hard on the stomach (such as nonsteroidal anti-inflammatory medications), taking high doses of arginine might stress the stomach additionally.

High doses of arginine should be used only under physician supervision in persons also taking medications that can alter the balance of potassium in the body (such as potassium-sparing diuretics or ACE inhibitors). For persons taking transdermal nitroglycerin, arginine may help prevent the development of tolerance.

Bibliography

Baecker, N., et al. “L-Arginine, the Natural Precursor of NO, Is Not Effective for Preventing Bone Loss in Postmenopausal Women.” Journal of Bone and Mineral Research 20 (2005): 471-479.

Bednarz, B., et al. “Efficacy and Safety of Oral L-Arginine in Acute Myocardial Infarction.” Kardiologia polska 62 (2005): 421-427.

Grasemann, H., et al. “Oral L-Arginine Supplementation in Cystic Fibrosis Patients.” European Respiratory Journal 25 (2005): 62-68.

Ito, T. Y., et al. “The Enhancement of Female Sexual Function with ArginMax, a Nutritional Supplement, Among Women Differing in Menopausal Status.” Journal of Sex and Marital Therapy 32 (2006): 369-378.

Mansoor, J. K., et al. “L-Arginine Supplementation Enhances Exhaled NO, Breath Condensate VEGF, and Headache at 4342 m.” High Altitude Medicine and Biology 6 (2005): 289-300.

Moriguti, J. C., et al. “Effects of Arginine Supplementation on the Humoral and Innate Immune Response of Older People.” European Journal of Clinical Nutrition 59 (2005): 1362-1366.

Stanislavov, R., and V. Nikolova. “Treatment of Erectile Dysfunction with Pycnogenol and L-Arginine.” Journal of Sex and Marital Therapy 29 (2003): 207-213.

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