L-arginine is a semi-essential proteinogenic amino acid whose effectiveness has been thoroughly researched. Arginine stands out among other amino acids as it has the highest concentration of the important molecule nitrogen (“N”). The presence of nitrogen separates amino acids from the other two energy suppliers, carbohydrates and fats, which do not contain nitrogen.
Arginine plays an important role in vascular regulation, the immune system, production of the body’s insulin, and development of male spermine. The intake of L-arginine is particularly important during growth phases or periods of illness. For this reason, L-arginine is increasingly categorized as an indispensable or essential amino acid.
In the body, L-arginine is quickly converted to ornithine. It is therefore possible to replace L-arginine with ornithine. However, there are no proven advantages to taking ornithine instead of arginine. Moreover, ornithine has not been studied nearly as much as arginine.
What are the functions of L-arginine in the body?
- Nitric oxide (NO) is formed from arginine. NO plays an important role in regulating blood pressure and circulation. It has positive effects on high blood pressure and also increases potency.
- Arginine is an important factor for the immune system.
- Spermine and spermidine are formed from L-arginine. It is thus important for the development of sperm.
- It has an important role in the urea cycle: detoxes the body.
- L-arginine is important for building the body’s protein and collagen.
- It is part of the body’s own hormone synthesis (including insulin, norepinephrine).
The recommended dosage ranges from 3,000 mg to 8,000 mg. Athletes sometimes take a higher dosage of 30,000 mg on a short-term basis.
Taking L-arginine in combination with plant-based substances such as hawthorn, grape seed extract, or green tea supports circulation in cases of atherosclerosis, low blood pressure, or erectile dysfunction. What all these ingredients have in common are procyanidins which are known for their heart strengthening qualities and also improve circulation. Taking additional B vitamins (B6, folic acid, B12) is also recommended. These vitamins help reduce blood vessel damaging homocysteine levels.
Formula: C6H14N4O2 (or C6H14N4O2·HCL as l-arginine HCL)
Abbreviation: Arg or R
Properties: white, crystalline powder. Basic. Very water soluble but has a bitter taste.
Origin: Due to cost considerations, in industrial production arginine is made from plant-based raw materials via a fermentation process. L-arginine as a nutritional supplement is therefore generally always plant-based.
Biosynthesis: in the urea cycle L-arginine is converted to L-ornithine, L-aspartate, and carbamoyl phosphate.
Side effects are rare even at a dosage of 30 grams per day. However, the stomach sometimes requires time to adjust to such quantities of pure L-arginine. Daily doses should be started at a lower quantity and increased gradually.
In active Herpes, taking L-arginine may lead to a worsening of symptoms. L-arginine should be taken in combination with lysine in these cases.
Taking L-arginine may significantly increase the effects of medications that lower blood pressure or affect nitric oxide metabolism (such as PDE5 inhibitors found in drugs to treat erectile dysfunction like Viagra®, Levitra®, or Cialis®).
Walnuts, pine nuts, and pumpkin seeds contain approx. 15% L-arginine. By comparison, the content of arginine in proteins from chicken, pork, or fish is around three to seven percent. Protein from peas contains significantly more L-arginine than milk protein.
Daily requirements of arginine
A balanced diet provides approx. 1,000 mg – 5,000 mg of bound arginine. Additionally, the body can produce small amounts through the urea cycle. However, for intense athletic activity, diseases ( including atherosclerosis, erectile dysfunction, high blood pressure), or when recuperating from an injury, these amounts may be insufficient.
Your body’s requirements for L-arginine increase as you age: this is because the level of L-arginine’s physiological antagonist, ADMA (asymmetric dimethylarginine) increases fourfold. 1 ADMA neutralizes the properties of L-arginine. Many nutritionists therefore recommend taking 3,000 mg – 5,000 mg of supplemental L-arginine daily. 2
L-arginine in Food
Many proteins only contain approx. 3% – 5% L-arginine. Nuts and seeds contain the most L-arginine. Walnuts, pumpkin seeds, and pine nuts have an L-arginine content between 10% and 15%.
Milk proteins contain relatively little L-arginine. Taking supplemental pure arginine can thus improve the biological value of milk protein (whey protein, casein). The amount should be approx. 4 – 5 grams pure L-arginine per 100 grams of whey protein or casein.
Effects of L-arginine and metabolism
Atherosclerosis, High Blood Pressure
A lot of research has been conducted to study the effects of L-arginine on the vascular system and blood pressure. Since L-arginine is the only originator for the molecule nitric oxide (NO), which has vascular control properties, it plays a role in improving the flexibility of blood vessels. It thus helps the body improve the natural regulation of blood pressure.
A well-recognized meta analysis dating from 2009 confirmed this effect (a meta analysis is a quantitative statistical analysis of many studies on the same subject): the supplemental intake of L-arginine helped improve circulation in small blood vessels.3
Another meta analysis published in 2011 also confirmed the results: L-arginine significantly helps reduce blood pressure in patients with hypertension.4
A large-scale German study concluded that the combination of 2,700 mg arginine with folic acid (vitamin B9), vitamin B6, and Vitamin B12 improved circulatory disorders and blood pressure regulation. The three B vitamins had the effect of reducing homocysteine levels, which can be damaging to blood vessels.
L-arginine also supports blood flow characteristics and helps prevent the development of blood clots. This effect was achieved with a dose of 7 grams – 8 grams per day. 5
Help with erectile dysfunction
Erectile dysfunction in men is often related to blood circulation problems. The flexibility of blood vessels is increasingly compromised with age. This is because not enough of the necessary molecules that affect vessel dilation reach the interior cell walls. With L-arginine the generation process of NO, an important molecule in vessel dilation control, can be improved.
Several studies in which men took supplemental L-arginine alone (mostly as L-arginine HCL, partly as L-arginine aspartate or L-arginine base – the form it was taken in did not seem to have a material effect) did not provide clear results. In general, some improvement in erectile function was recorded. A dose of 5,000 mg achieved better results than a dose of just 3,000 mg or less. 6
Several follow-up studies found that combining L-arginine with pine bark extract brought forth better results. The extract from the French coastal pine contains many proanthocyanidins and catechins that can significantly improve blood vessel dilation.
Taking a combination of L-arginine and pine bark extract resulted in improved erectile function in 90% of the study participants. Taking L-arginine alone only achieved success in 50% of the participants.
Sperm development (spermine, spermidine) requires substantial amounts of l-arginine. An American study concluded that the supplemental intake of 4,000 mg L-arginine daily results in significant improvement in the number and a concentration of motile sperm. 7 These results were confirmed by an Italian study in which participants took a dose of 8,000 mg of L-arginine daily. 8
Several Austrian studies show that the combination of L-arginine with carnitine, acetyl-L-cysteine, and antioxidants (vitamin C, vitamin E, selenium) doubled both the number and the motility of sperm in men with limited fertility. 9
The two effects with regard to the number and concentration of motile sperm build on one another. The end result is that the number of sperm capable of fertilizing an egg can be increased by a factor of four through therapy with various antioxidants and arginine.
In the studies utilizing the combination products, the micro-nutrients were administered in small doses. For example, only 500 mg of L-arginine a day. Because of the low dosage, the combination was also extremely well tolerated by the participants.
Insulin Sensitivity, Regulation of Blood Sugar Levels
Diabetics have decreased sensitivity to insulin, or, in other words, their resistance to insulin is increased. This means that cells no longer recognize the body’s own hormone, insulin, and that available insulin is no longer properly absorbed.
In higher dosages between 6,000 mg to 10,000 mg daily, L-arginine appears to have a regulating influence on insulin sensitivity. 10
In a study conducted in 2001, insulin sensitivity was increased by 30% through the intake of arginine. 11
Immune System and Wound Healing
L-arginine is an element of the immune system. 12 One study showed that taking L-arginine strengthens the immune system: the number of lymphocytes was increased, and the activity of phagocytes and NK cells was improved. Moreover, arginine supports the development of Interleukin 1, an important messenger in the immune system. 13 Another study evidenced the same positive effects on central immune function in cancer patients. 14. There are also indications that wound healing is accelerated with L-arginine supplementation. 15
Arginine is therefore recommended especially for diets (compromised immune system due to low food absorption) following surgeries and during intense sport activity. However, arginine can also achieve increased activity of the immune system in healthy individuals (increased cell division by 200% in lymphocytes). 16
The roots of hair are supplied with nutrients by very small blood vessels. Even the slightest damage to the vessels can result in deficiencies. Hair growth slows, and the fullness of hair is reduced. Sustained nutrient deficiency of the hair root leads to hair loss.
Due to its blood vessel dilating effects, L-arginine may help stimulate nutrient supply to hair roots. Initial studies suggest that L-arginine has this positive effect.17.
Whether externally-applied L-arginine supports a full head of hear (in a shampoo for instance) remains to be seen. Currently, it is assumed that L-arginine cannot be absorbed through the skin.
Strength Training, Perfusion of Muscle
The positive effects of L-arginine on circulation are also recognized by athletes. Because with improved circulation muscles, too, are supplied with more oxygen and nutrients. Also, muscle mass may be slightly increased through improved perfusion. Bodybuilders refer to this effect as “pumped“.
There have been various, non-conclusive results in studies that suggest the release of growth hormones due to the intake of L-arginine. The amount that would potentially cause a measurable result lies somewhere around 12,000 mg and higher. Supplementation must therefore strictly adhere to guidelines. 18 You can find more information on this topic in the chapter “Building Muscle“.
Side Effects of L-Arginine
Arginine is approved as a nutritional supplement and is a safe amino acid to ingest. Dosages that exceed 10,000 mg a day may lead to slight irritations of the stomach and intestinal tract. These irritations generally go away once the digestive tract has grown accustomed to the supplementary amount of L-arginine. In rare cases, sleep disturbances are reported with dosages in excess of 10,000 mg.
In existing Herpes infections, taking L-arginine may lead to worsening symptoms. It is suspected that this is a result of L-arginine’s effects on the immune system. Combining L-arginine with lysine can significantly reduce the Herpes activating effects as lysine may reduce the proliferation of the Herpes virus.
Very high amounts of L-arginine, in excess of 15,000 mg per day, may also have a dehydrating effect. Therefore, it is recommended that dosages over 7,000 mg are spread across several times a day.
In animal testing, L-arginine has proven toxic at doses of 5 – 12 grams per kg of body weight. For humans, this translates to approx. one half to one kilogram L-arginine per day.
Due its properties, L-arginine may increase the effects of medications to treat high blood pressure and erectile dysfunction. If you are taking any of these medications, you should consult your physician or pharmacist before supplementing with L-arginine.
- K. SydowR. H. Böger: Reloaded: ADMA and oxidative stress are responsible for endothelial dysfunction in hyperhomocyst(e)inaemia: effects of L-arginine and B vitamins. In: Cardiovasc. Res., 2012, doi:10.1093/cvr/cvs205 ↩
- Robenek, H.; “Arteriosklerose, Herzinfarkt, Schlaganfall. Therapeutisches Potential von L-Arginin”; 7. Aufl. 2013; S. 7 (“Atherosclerosis, Heart Infarct, Stroke. Therapeutic Potential of L-Arginine”; 7th Edition. 2013.; p. 7) ↩
- Bai Y, Sun L, Yang T, Sun K, Chen J, Hui R.; “Increase in fasting vascular endothelial function after short-term oral L-arginine is effective when baseline flow-mediated dilation is low: a meta-analysis of randomized controlled trials.”; Am J Clin Nutr. 2009 Jan;89(1):77-84. doi: 10.3945/ajcn.2008.26544. Epub 2008 Dec 3; http://www.ncbi.nlm.nih.gov/pubmed/19056561 ↩
- Dong Y, In Q, Hang Z, Chao Y, Wang J, Arizonian F, Hang W.; “Effect of oral L-arginine supplementation on blood pressure: a meta-analysis of randomized, double-blind, placebo-controlled trials.”; Am Heart J. 2011 Dec;162(6):959-65. doi: 10.1016/j.ah.2011.09.012. Epub 2011 Nov 8.; http://www.ncbi.nlm.nih.gov/pubmed/22137067 ↩
- Wolf, A., Zalpour, C., et al. “Dietary L-Arginine supplementation normalizes platelet aggregation in hypercholesterolemic humans”, J Am Coll Cardiol, 1997, 29: pp. 419-425 ↩
- Chen J, Wollman Y, Chernichovsky T, Iaina A, Sofer M, Matzkin H.; “Effect of oral administration of high-dose nitric oxide donor L-arginine in men with organic erectile dysfunction: results of a double-blind, randomized, placebo-controlled study.”; BJU Int.; 1999 Feb;83(3):269-73. ↩
- Schachter A, Goldman JA, Zukerman Z.; “Treatment of oligospermia with the amino acid arginine.” J Urol 1973;110:311-313. ↩
- Scibona M, Meschini P, Capparelli S, et al.; “Larginine and male infertility.” Minerva Urol Nefrol 1994;46:251-253. ↩
- Imhof, M. et al.; “Mikronährstoffe in der Fertilitätsbehandlung: Klinische Ergebnisse”; Journal für Urologie und Urogynäkologie 2009; 16 (Sonderheft 5) (Ausgabe für Österreich), 19-20 (“Micronutrients in Fertility Treatment: Clinical Results, Journal for Urology and Urogynecology 2009; 16 (Special Edition 5) (Austrian Edition), 19-20 ↩
- Lucotti, P., et al.; “Beneficial effects of a long-term oral L-Arginine treatment added to a hypocaloric diet and exercise training program in obese, insulin resistant type 2 diabetic patients”; American Journal of Physiological Endocrinology and Metabolism; 2006; 291 (5): E906-912 ↩
- Piatti, P.M., Monti, L.D., et al.; “Long-term oral L-arginine administration improves peripheral and hepatic insulin sensitivity in type 2 diabetic patients”; Diabetes Care; 2001; Volume 24, issue 5, S. 875-880 ↩
- Stechmiller, J.K.; “Arginine supplementation and wound healing. Nutritional Clinical Practise; 2005; 20(1): 52-61 ↩
- Reynolds, JV, Daly, JM, et al.; “Immunomodulatory effect of Arginine”; Surgery, 1988; 104(2): 141-151 ↩
- Brittenden, J., Park, KG, “L-Arginine stimulates host defenses in patients with breast cancer”; Surgery, 1994; p115(2), p. 205-212 ↩
- Lu, SL, “Effect of arginine supplementation on T-lymphocyte function in burn patients” Zhonghua Zhen Xing, 1993, 9(5), p. 368-371 ↩
- Barbul, A., Sisto, DA, et al. “Arginine stimulates immune response in healthy human beings”, Surgery, 1981, 90: p. 244 ↩
- Saini, R. & Zanwar, A. A.; “Arginine Derived Nitric Oxide: Key to Healthy Skin”; Bioactive Dietary Factors and Plant Extracts in Dermatology; 2013, pp. 73-82 ↩
- Burgerstein et al.; “Handbuch Nährstoffe” (Nutrients Manual); 2013; S. 261 ↩