Do L-Arginine Supplements Have Benefits? 2,763 Clinical Studies Reviewed

Introduction

L-Arginine is described as an ‘ergogenic’ or all-around ‘mojo booster’ in plain English. It is marketed as an anti-ageing agent, sexual booster, and sports endurance agent.

Fact or fiction?

Let’s look at the evidence.

What Is L-Arginine?

Arginine was discovered back in 1886 by a Swiss chemist (Ernst Schulze), who isolated it from a lupine seedling.

L-Arginine is a dibasic amino acid. It is a precursor to a number of important biochemical reactions. It is classified as both a non-essential and semi-essential amino acid (depending on which paper you read).

Both terms are technically correct. It’s all a question of context.

Non-essential means that the body does not rely on external sources of L-Arginine, which is true for normal healthy adults who can synthesize L-Arginine de novo from glutamine, glutamate, and proline.

Semi-essential means that it is only needed sometimes. During times of high metabolic demand (e.g. critical illness), the endogenous synthesis of L-Arginine may be insufficient to meet the requirements of the body.

Oral supplementation with L-Arginine in the form of dietary supplements or functional foods is growing in popularity. The theory (aka marketing spin) is that L-Arginine supplementation confers health benefits over and above the normal dietary intake.

L-Arginine is pleiotropic in terms of its mechanisms of action.

It modulates L-Citrulline and thereby reduces platelet aggregation.

It also modulates nitric oxide via the guanyl cyclase system and relaxes smooth muscle.

Zinc is an essential co-factor for the optimum functioning of L-Arginine.

There are three main sources of L-Arginine:

  1. food
  2. recycling of body proteins
  3. and via conversion of citrulline in the kidney.

Amazon offers over 1,000 L-Arginine products, and the average cost of 1,000mg of L-Arginine is $0.10.

Can You Get L-Arginine From Food?

The average daily intake of L-Arginine is 5gm. Dietary sources include protein-rich foods, including:

  • nuts (peanuts and walnuts)
  • animal products (dairy and pork)
  • seafood
  • legumes (soybeans) and
  • chocolate.

Here are examples of the average L-Arginine content for some of your favorite foods:

  • turkey breast 16 gms
  • soybeans 1 cup 5 gms
  • cheese 1.4 gms.

One review paper reviewed available human published data on L-Arginine and predicted that a dose of 20gm/day is the observed safe level dose for normal healthy adults (1).

The authors of the study add a big disclaimer and say that “the data behind the conclusion is not sufficient for a confident conclusion on long-term safety.” I am all in favor of being responsible and cautious, but this is a totally unhelpful paper.

Is There Any Research?

There are 100,000 publications related to L-Arginine, including 2,763 clinical trials. This is comparable to research on glutamate, which has 140,000 publications and 2,000 clinical trials.

Does L-Arginine Improve Heart Health?

There are numerous papers looking at L-Arginine for heart health.

A Cochrane review examined the effect of L-Arginine supplementation on blood pressure (2).

The reviewers identified 11 randomized, double-blind, placebo-controlled trials involving 387 patients. The meta-analysis found that oral L-Arginine significantly lowers both systolic and diastolic blood pressure. A Cochrane slam dunk.

A number of studies have shown that L-Arginine benefits patients with cardiac failure. A one-hour infusion of intravenous L-Arginine resulted in a significant increase in cardiac output in a small study of 11 patients with cardiac failure (3).

Bottom Line

There is clinical data to support a role for L-Arginine in heart health in select patient groups.

Does It Affect Ageing?

Vascular senescence (blood vessel ageing) manifests as heart disease and strokes. There is considerable interest in the potential role of L-Arginine as a nutritional prophylaxis against vascular senescence.

A comprehensive review article that was published in the Journal of Cardiovascular Pharmacol Therapeutics examined the available data on this topic (4). The article parsed 77 articles and concluded that L-Arginine confers no benefit and may adversely affect outcomes related to myocardial infarction in the following patient groups:

healthy and older individuals with preserved endothelial function, peripheral vascular disease, and chronic kidney injury.

L-Arginine may improve vascular function in patients with vascular endothelial dysfunction.

The final line of the article says it all: “Recommendations of L-Arginine as a general vascular panacea for all ageing persons is not warranted at this time and the quest for the fountain of youth should continue.” Ouch.

Asymmetric dimethyl arginine (ADMA) is a competitive inhibitor of L-Arginine metabolism and appears to determine an individual’s response to L-Arginine (5).

L-Arginine appears to exert no effect in people with low ADMA levels. L-Arginine restores the L-Arginine/ADMA balance in people with high levels of ADMA and thereby normalizes endothelial function. That seems to make sense to me.

Bottom Line

L-Arginine is not an anti-ageing panacea (to quote the experts).

Does It Increase Exercise Performance?

There is significant interest in the ‘ergogenic’ potential of L-Arginine (mojo booster).

A meta-analysis of 2,687 articles showed that L-Arginine supplementation provided little enhancement of athletic performance or improvements in recovery (6).

The authors were specifically interested in data in military personnel and found no data in this demographic.

Another review paper published in Sports Medicine also evaluated the medical literature on exercise performance after L-Arginine supplementation (7).

This review found that acute dosing with L-Arginine improved exercise performance in three out of five relevant studies. Chronic L-Arginine dosing enhanced exercise performance in four out of eight studies reviewed. Not a slam dunk at all.

A study in 9 elite athletes compared L-Arginine plus nitrate versus nitrate versus placebo and found that there were no differences during sub-maximal running, 5km performance, and cross-country skiing (8).

Bottom Line

There is no conclusive proof that L-Arginine helps in exercise or sports endurance.

Does It Help the Immune System?

A meta-analysis of all the clinical trials investigating the effects of L-Arginine on the immune system was published in 2014 (9).

Out of a total of 1,297 studies and papers identified by the reviewers, 11 studies met the inclusion criteria for this meta-analysis. The reviewers concluded that L-Arginine provides some improvement in some aspects of immune function but that larger well-designed clinical trials are required.

There are some interesting studies in patients with HIV infection which are worthy of a special mention.

A double-blind placebo-controlled pilot study randomized 11 HIV-infected and virally suppressed adults (HIV viral load < 10,000 copies per ml) to L-Arginine 19.6 g or a placebo daily to assess the role (if any) of L-Arginine on immune function in HIV disease (10).

The number-one rule in any clinical study is ‘do no harm.’ From an HIV perspective, this means that any new intervention should not impact on the level of circulating HIV in the plasma. There is a direct correlation between HIV viral load levels and morbidity and mortality in HIV-infected individuals.

Following 14 days of L-Arginine, all patients remind virally suppressed. The L-Arginine was well tolerated. However, there were no statically significant improvements in natural killer cell function in this short-term pilot study.

A second study in 64 HIV-infected patients from the Swiss Cohort study found that 6 months of omega-3 plus L-Arginine did not improve immunological parameters (11).

Bottom Line

There is no clear evidence to support a role for L-Arginine in any specific immune deficiency.

Regardless of the data, the immune system is extremely complex, and it is way too simplistic to talk about anything helping the ‘immune system’ as if it were a single entity.

Does It Treat Erectile Dysfunction? Infertility?

A double-blind study from Japan evaluated the effect of a combination product containing Pycnogenol 60mg, L-Arginine 960mg, and aspartic acid 552mg daily versus a matched placebo in men with mild to moderate erectile dysfunction (12).

The study took place over 8 weeks. Study subjects reported no adverse events and improved erectile function and sexual satisfaction in the active arm of the study.

Similar results were reported for Pycnogenol and L-Arginine from a 50-patient study in Bulgaria (13).

L-Arginine supplementation improved conception rates in a single study in women undergoing in vitro fertilization (14).

L-Arginine is required for normal spermatogenesis. L-Arginine-deficient diets for as little as nine days can reduce sperm counts by 90% and increase the non-motile sperm ten-fold. Oral L-Arginine supplementation has been shown to increase sperm counts and motility, provided that the baseline sperm count is over 10,000,000/ml. (15).

Bottom Line

L-Arginine is biologically plausible as a pro-fertility agent, which is backed up by some small clinical trials.

Is L-Arginine Supplementation Safe?

The longest study on L-Arginine was done in 66 renal transplant patients who received L-Arginine for a minimum of three years (16). No adverse events were noted.

The largest clinical trial involving L-Arginine looked at 792 patients post myocardial infarction who received 9gm L-Arginine for 30 days, and no significant adverse events were noted (17).

Some cancers (hepatocellular, breast, and endometrial) may be stimulated by L-Arginine. L-Arginine-deprived diets are an unproven therapeutic modality in patients with these malignancies. Even though L-Arginine deprivation has not been proven to help these malignancies, it seems prudent to avoid L-Arginine in these patients for now.

It is generally recommended that people taking medications for blood pressure take care with L-Arginine, as it may cause their BP to fall too low.

L-Arginine may also cause reactivation of the herpes simplex virus.

Conclusion

L-Arginine is tightly controlled by the body, and there is absolutely no evidence to support a role for supra-physiological levels of L-Arginine in normal, healthy people.

There is evidence to support a role for L-Arginine in select patient populations, i.e. when patients tip over in their metabolic requirement for L-Arginine and it becomes semi-essential.

As per its classification, L-Arginine is either non-essential or semi-essential and not ‘design your optimal body’ essential.

As the journal article says, ‘the search for the fountain of youth should continue’ and maybe we should just stop trying to ‘game or out-smart nature’ and simply enjoy life.

References

  1. Risk assessment for the amino acids taurine, L-glutamine and L-arginine.
    Shao A, et al. Regul Toxicol Pharmacol. 2008
  2. Effect of oral L-arginine supplementation on blood pressure: a meta-analysis of randomized, double-blind, placebo-controlled trials. Dong JY, et al. Am Heart J. 2011
  3. Improvement of cardiac performance by intravenous infusion of L-arginine in patients with moderate congestive heart failure. Clinical trial Koifman B, et al. J Am Coll Cardiol. 1995
  4. L-arginine as a nutritional prophylaxis against vascular endothelial dysfunction with aging. Heffernan KS, Fahs CA, Ranadive SM, Patvardhan EA. J Cardiovasc Pharmacol Ther. 2010 Mar;15(1):17-23. doi: 10.1177/1074248409354599. Epub 2010 Jan 6.
  5. The pharmacodynamics of L-arginine.
    Review article Böger RH, et al. Altern Ther Health Med. 2014
  6. Safety and performance benefits of arginine supplements for military personnel: a systematic review.
    Review article Brooks JR, et al. Nutr Rev. 2016
  7. L-Arginine as a potential ergogenic aid in healthy subjects.
    Review article Álvares TS, et al. Sports Med. 2011
  8. Effects of acute supplementation of L-arginine and nitrate on endurance and sprint performance in elite athletes.
    Randomized controlled trial Sandbakk SB, et al. Nitric Oxide. 2015
  9. Effect of L-arginine on immune function: a meta-analysis.Kang K, et al. Asia Pac J Clin Nutr. 2014
  10. A pilot study of the safety and efficacy of supplemental arginine to enhance immune function in persons with HIV/AIDS.
    Randomized controlled trial Swanson B, et al. Nutrition. 2002
  11. A randomized double-blind controlled study of 6 months of oral nutritional supplementation with arginine and omega-3 fatty acids in HIV-infected patients. Swiss HIV Cohort Study.
    Randomized controlled trial Pichard C, et al. AIDS. 1998
  12. Clinical assessment of a supplement of Pycnogenol® and L-arginine in Japanese patients with mild to moderate erectile dysfunction. Clinical trial Aoki H, et al. Phytother Res. 2012
  13. Improvement of erectile function with Prelox: a randomized, double-blind, placebo-controlled, crossover trial.
    Randomized controlled trial Stanislavov R, et al. Int J Impot Res. 2008
  14. Adjuvant L-arginine treatment for in-vitro fertilization in poor responder patients.
    Randomized controlled trial Battaglia C, et al. Hum Reprod. 1999
  15. Arginine: Clinical potential of a semi-essential amino acid.. Review article Appleton J, et al. Altern Med Rev. 2002
  16. The influence of immunomodulatory diets on transplant success and complications. Randomized controlled trial Alexander JW, et al. Transplantation. 2005
  17. L-arginine supplementation prolongs exercise capacity in congestive heart failure. Randomized controlled trial Bednarz B, et al. Kardiol Pol. 2004. Article in English, Polish.
Summary
Do L-Arginine Supplements Have Benefits? 2763 Clinical Studies Reviewed
Article Name
Do L-Arginine Supplements Have Benefits? 2763 Clinical Studies Reviewed
Author
Healthy But Smart

Leave a Reply

Your email address will not be published. Required fields are marked *