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Product Review: Review of L-Arginine Supplements |
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Initial Posting: 8/25/17 Last Update: 3/20/18
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Summary:
- What is it? L-arginine (or arginine) is an amino acid which is necessary for the body's production of nitric oxide, a compound that relaxes blood vessels and allows more blood to flow through arteries. The form in supplements is typically "free form" arginine, but is sometimes a compound, such as L-arginine HCl. (See What It Is). Not all labels clearly list the amount of arginine. (See What to Consider When Buying), but you can use the Results table to easily compare amounts of arginine in tested supplements.
- What does it do? L-arginine may modestly improve symptoms, such as exercise intolerance, in congestive heart failure, angina, and leg pain due to intermittent claudication, as well as exercise endurance in recreational and older athletes. Some, but not all, studies have shown some modest benefits in sexual dysfunction and Raynaud's syndrome (See What It Does).
- How much to take? Dosage depends on the condition being treated, but is typically several thousand milligrams per day (See Dosage).
- Best choice? Among the products that passed our laboratory tests (See What CL Found), we selected Top Picks for arginine for general use, cardiovascular, sexual enhancement, and sport.
- Cautions: L-arginine supplementation appears to be generally safe and well tolerated in healthy individuals, although stomach upset may occur. L-arginine may interact with blood-pressure lowering and diabetes medications. Do not use if you have had a heart attack, and do not use to treat serious conditions including congestive heart failure, angina, or intermittent claudication without physician supervision. For details, see Concerns and Cautions.
What It Is:
L-arginine, also referred to as arginine, is an amino acid required to carry out the synthesis of nitric oxide, a compound that, working through the compound cGMP, relaxes blood vessels and allows more blood to flow through arteries. It has been hypothesized that taking extra arginine will increase nitric oxide levels and, in turn, increase blood flow to various parts of the body.
What It Does: (See the CL Encyclopedia article on Arginine for more details)
Arginine has been clinically studies for a variety of conditions relating to blood flow, Results have been mixed, and arginine may be less helpful to people who are well-nourished.
Note: The first three conditions listed below are life-threatening. If you have angina, congestive heart failure, or intermittent claudication, do not attempt to treat yourself with arginine except under physician's supervision.
Congestive Heart Failure (fluid build-up in lungs and legs due to heart weakness)
Several small clinical trials have shown that arginine at doses of 5 grams to 15 grams (1 gram = 1,000 mg) daily may improve symptoms of congestive heart failure as well as objective measures of heart function (Hambrecht, J Am Coll Cardiol 2000).
Angina (chest pain due to reduce blood flow to heart)
Studies have shown improvement in exercise tolerance, although not heart function, in people with angina when taking 6 grams per day of arginine. (Bednarz Int J Cardiol 2000). Another study showed decreased symptoms of angina when 6.6 grams of arginine was taken daily (from a fortified food bar with vitamins and minerals) (Maxwell,J Am Coll Cardiol 2002).
Intermittent Claudication (leg pain during exercise due to insufficient blood flow)
A study showed that 2 weeks of treatment with 6.6 grams of arginine daily (from a fortified food bar with vitamins and minerals) improved walking distance by 66% (Maxwell, Vasc Med 2000). However, a longer (6-month) and better designed study (Wilson, Circulation 2007) found arginine (3 grams per day) to be less effective than placebo.
Raynaud's phenomenon
Because L-arginine is involved in the synthesis of nitric oxide (a compound which relaxed blood vessels and allows more blood to flow through them), it is sometimes promoted for this use. A few case reports (Rembold, Mol Cell Biochem 2003) and preliminary studies have suggested a benefit in certain people. For example, one very small study found that a dose of 4 grams of L-arginine taken twice daily was helpful for Raynaud's phenomenon associated with systemic sclerosis, but not for primary Raynaud's phenomenon (not caused by another disease/condition); however, this study did not include a placebo, so it's not possible to determine whether L-arginine was truly effective (Agostoni, Int J Clin Lab Res 1991). A study (noted in the Encyclopedia article about Raynaud's phenomenon) which used the same dose of L-arginine and did include a placebo found no benefit for primary Raynaud's phenomenon (Khan, Arthritis Rheum 1997).
Sexual Enhancement (See Product Review of Sexual Enhancement Supplements for more information)
It has been hypothesized that taking high levels of arginine could increase blood flow to the genitals during arousal by increasing nitric oxide levels. However, in some pharmaceutical studies leading up to the creation of Viagra, drugs that increased the levels of nitric oxide in the penis were not found to be effective; rather, it was found necessary to increase sensitivity to the rise of nitric oxide. The body may simply accommodate to higher background levels of nitric oxide.
Nevertheless, arginine might offer modest benefit for sexual dysfunction in men. A double-blind, placebo controlled trial of 50 men with erectile dysfunction tested arginine at a dose of 5,000 mg per day for six weeks. About a third of the participants who received arginine showed improvement. For comparison, 11% of men taking a placebo said they also noticed an improvement (Chen, BJU Int 1999).
Although arginine alone has not been studied as a treatment for sexual dysfunction in women, a small but reasonably good double-blind trial found evidence for benefit with a combination formula (ArginMax for Women — tested in this Review) providing a daily dose of 2,500 mg of an L-arginine "proprietary blend", as well as amounts of Panax ginseng, Ginkgo biloba extract, damiana, plus numerous vitamins and minerals. In the four-week, double-blind study, 77 women with decreased libido were given either the combination product (ArginMax) or placebo. Over 70% of the women taking ArginMax reported an increase in sexual desire, compared with over 40% of women taking a placebo. (The placebo effect is notoriously strong for such conditions. Simply believing that a pill will increase desire or satisfaction can become a self-fulfilling prophecy.) Other reported benefits included: relative satisfaction with sex life (74% vs. 37%), improved frequency of orgasms (47% vs. 30%), and improved clitoral sensation (53% vs. 35%). No significant side effects were seen. (Ito, J Sex Marital Ther 2001).
There have been other studies of arginine for sexual dysfunction in women, but because they were not double-blind, placebo-controlled trials, they are of little scientific value.
Pressure Ulcers (Bed Sores)
Arginine supplementation has shown possible benefit for treating pressure ulcers based on studies in which it has been given in combination with other vitamins/minerals. In a review of 4 randomized trials, it was associated with improvement in some parameters of healing, although not with a statistically significant improvement in ulcer size. One study among people who were not malnourished found no benefit compared to placebo. (Langer, Cochrane Database Syst Rev 2014).
Cancer
In women with breast cancer, 30 grams of L-arginine taken for 3 days prior to chemotherapy did not improve the response rate to the treatment compared to women who received a placebo -- although it did improve the response rate in the subset of women whose tumors were smaller than 6 cm (88% vs 52% with placebo, respectively) (Heys, Int J Oncol 1998). The same dose has significantly improved certain immune responses in women with breast cancer (Brittenden, Surgery 1994) and slowed tumor activity in people with non-cancerous colorectal tumors and decreased a marker of tumor progression in people with cancerous colorectal tumors (Ma, Clin Cancer Res 2007).
Be aware that certain types of cancer are especially dependent on arginine to grow — including melanoma and hepatocellular carcinoma -- and drug treatments that help to break down and eliminate arginine are being investigated as treatments (Phillips, Cancer Res Treat 2013). For people with these types of cancers, arginine supplementation would not seem advisable.
Exercise Endurance and Recovery
L-arginine may modestly increase exercise endurance in recreational and older athletes. However, it has not been shown to improve exercise performance or recovery from resistance exercise in trained athletes or active, young individuals. For example, a small study in Brazil among healthy, active young men and women found that a single dose of L-arginine (6 grams L-arginine dissolved in water) taken one hour before high-intensity resistance exercise did not decrease muscle fatigue, muscle soreness, blood lactate levels, or levels of a marker of muscle damage (creatine kinase) compared to placebo (Andrade, Appl Physiol Nutr Metab 2018).
L-arginine is widely promoted as a key ingredient in "nitric oxide" supplements, which are touted as increasing muscle size, but clinical evidence does not support this use. (See the Nitric Oxide Supplements Review Article for more information.)
There is mixed evidence as whether citrulline - an amino acid which is efficiently converted into L-arginine, may offer some performance benefit. In a study of ten healthy, recreationally-active young men who took either 6,000 mg of L-arginine, 6,000 mg of citrulline, or placebo for seven days, both L-arginine and citrulline caused similar increases in blood levels of arginine, but only citrulline supplementation improved exercise tolerance (by 12%) and increased the total amount of work completed (by 7%) during a severe-intensity cycling exercise test compared to placebo (Bailey, J Appl Physiol 2015). However, a study of 12 recreationally trained young men and women (average age 24) found that a single dose of 8,000 mg of citrulline malate (L-Citrulline DL-Malate, Bulk Supplements) -- providing 5,333 mg of citrulline -- mixed into water and taken one hour before high intensity exercise did not improve performance or decrease fatigue compared to placebo (Farney, J Strength Cond Res 2017).
Other Uses
Some evidence suggests that arginine may be helpful in AIDS-related wasting, colds, necrotizing enterocolitis, intolerance to nitrate medication, post-surgery recovery and in improving kidney function in kidney transplant patients treated with cyclosporine. There is also preliminary evidence of a role for arginine in treating other conditions, including senile dementia, hypertension, and sickle cell disease.
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