What is arginine?
L-Arginine is an alpha amino acid which is among the 20 most commonly found amino acids in the human body. Nobel Prize-winning clinical research has demonstrated that it has significant health benefits by improving blood flow (circulation) throughout the body.
Arginine is known as a semi essential amino acid, due to the fact that the body naturally produces it1. However depending on the particular health of an individual, the benefits of supplementing this amino acid are significant.
Arginine is naturally synthesised through a biosynthetic pathway involving exchange of urea. The precursor of arginine is another amino acid known as citrulline.
The body produces Citrulline from glutamine and glutamate using certain cytosolic enzymes such as argininosuccinate synthetase (ASS) and argininosuccinate lyase (ASL). This Citrulline is converted into Arginine by the proximal tubule cells of the kidney.
Other cells of the body also produce small amounts of arginine from citrulline. However, despite arginine synthesis occuring naturally, the amounts of this amino acid produced are generally insufficient to meet the recommended daily intake of around 2 to 5 grams2.
The benefits of L-arginine to the body have been well documented in hundreds of clinical studies of several decades. As a result Arginine is highly recommended as a dietary supplement. The Nitric Oxide (NO) Synthase family of enzymes catalyse the formation of Nitric Oxide from an L-Arginine precursor.
Nitric Oxide has a range of important functions, including as a neurotransmitter to transmit nerve impulse across a synapse. It also
- helps regulate vascular tone, reducing blood pressure3
- increases secretion of the blood glucose lowering hormone insulin4,
- promotes angiogenesis which is the formation of new blood vessels5,
- it beneficially supports the immune system6and it
- plays some role in neural development7.
Nitric Oxide is a critical signalling molecule (neurotransmitter) in blood vessels. The inner endothelium lining of the vessels, known as the tunica intima, stimulates the smooth muscle layer of the blood vessels, called the tunica media, to relax. This causes the blood vessels to dilate and widen, which results in lowered blood pressure.
Studies have found that supplementing with L-Arginine can increase Nitric Oxide levels and thus lower blood pressure3. One study found that, compared to placebo patients, those who took L-Arginine experienced a drop in systolic blood pressure of 5.39 mm Hg and diastolic blood pressure by 2.66 mm Hg9.
Phosphocreatine, which is a phosphorylated molecule of creatine, can rapidly supply their phosphate groups to Adenosine Diphosphate (ADP) molecules, converting them into Adenosine Triphosphate (ATP). This occurs in the 10 or so seconds following an intense muscular or neuronal exertion, such as during sport or weight lifting.
Erectile dysfunction, also known as impotence, is the impaired erectile function in sexually mature males. Proper blood flow to the sex organs is essential during sexual intercourse, and low levels of arginine in the body can have adverse effects. As previously mentioned, the synthesis of Nitric Oxide is dependent on arginine levels, which is an important chemical in maintaining the health of blood vessel linings.
Patients with low Nitric Oxide levels reported impaired sexual function, and in studies which supplemented them with high dosages of L-Arginine, both their Nitric Oxide levels as well as their sexual function significantly improved10.
The Nitric Oxide-enhancing effect has been shown particularly strong when Arginine is combined with Pine Bark Extract from the French maritime pine. Several clinical studies have found this nutrient combination beneficial in the long-term treatment of male potency problems.
Arteriosclerosis is a disease which results in stiffening of major arteries. This causes loss of elasticity as the tunica intima layer becomes more fibrous in nature, and the tunica media layer becomes calcified.
Asymmetric dimethylarginine (ADMA) is an endogenous and competitive inhibitor of nitric oxide synthase, which results in impaired synthesis of nitric oxide14. This interferes with endothelial function, and can lead to a specific type of arteriosclerosis known as atherosclerosis. ADMA is commonly considered to be a marker of vascular disease.
Arginine can block ADMA and preferentially react with Nitric oxide synthase enzymes, resulting in proper formation of Nitric Oxide and improved health of the blood vessel endothelium. As well as ADMA, another substance which promotes atherosclerosis is homocysteine.
This is a non-protein amino acid which increases oxidant stress, impairs endothelial function, and induces thrombosis, all of which are risk factors for cardiovascular disease15.
Elevated levels of homocysteine are usually cause by a B-vitamin deficiency. Studies show that L-arginine can reduce levels of homocysteine in the blood and hence lower its negative effects on the cardiovascular system16. Due to the vasodilating effects of Nitric Oxide, arginine supplementation is also used in patients with hypertension, or high blood pressure.
Diabetic patients can also experience some benefits from supplementing with arginine. It has been shown that arginine, in combination with glucose, can significantly increase the production of insulin from the pancreatic beta cells located in the islets of Langerhans.
Insulin is the hormone which stimulates peripheral cells, such as those of the skeletal muscle, to increase their cell membrane permeability to glucose. This results in a greater uptake of glucose into such cells, reducing levels of glucose present in the blood. Arginine takes effect on the beta cells by causing their cell membranes to depolarise17, which opens voltage gates Calcium channels.
The resulting influx of calcium ions cause the vesicles containing the insulin hormone to fuse with the cell membrane and be released out of the beta cells into the bloodstream. This increases blood insulin levels and can help people with both Type 1 and 2 diabetes.
Arginine also plays a role in maintaining the integrity of beta cells in the presence of cytokines, which are molecules that stimulate inflammation during an immune response18. By preventing the continued autoimmune destruction of beta cells, the production of insulin is maintained.
Mental stress and anxiety
Mental stress and anxiety can also be treated using arginine. In a double-blind placebo controlled study, the cortisol levels of subjects was significantly reduced, in turn helping manage stress levels19.
In 1998, the three scientists who fully revealed the signalling effects of Nitric Oxide on the blood vessels, recieved the Nobel Prize for Physiology and Medicine. L-Arginine is also a direct precursor to several other compounds such as urea and ornithine, citrulline, and glutamate. Creatine is also biosynthesised using arginine as an intermediate, which is an important substance in energy metabolism in cells.
Many companies are trying to capitalise on the health benefits of Arginine by selling supplements. These should be researched thoroughly, because some products are expensive and offer low dosages, whilst others are exceptionally good.
As the naturally synthesised amount of L-Arginine is often not enough to experience the full benefits of this substance, foods and supplements are recommended to help increase arginine levels within the body. Pork and chicken breast are fairly high in arginine, although during the cooking process some of this is lost.
Several types of nuts such as walnuts, cashew nuts and pine nuts are also rich in arginine. Certain species of fish such as tuna, anchovies and sardines have a relatively high arginine content20. However, despite certain foods being richer in arginine than others, the most effective way to increase arginine levels is through oral supplementation.
The required dosages of arginine supplementation in the treatment of medical conditions varies. Generally speaking, a minimum daily intake of 3000mg is recommended for noticeable results. For treatment of atherosclerosis and promotion of vascular health, as well as management of hypertension, between 3000mg and 5000mg is advised.
For diabetic complications, up to 9000mg has been taken daily, split up into three doses of 3000mg21. To treat erectile dysfunction, a minimum of 5000mg per day is required to see valid results.
When used at extremely high dosages of more than ten thousand milligrams per day, there can be some noticeable side effects. Some of these include stomach problems such as nausea, indigestion and bloating. Airway inflammations can also result, which can worsen asthma in current suffers. Imbalances in blood electrolytes such as potassium, phosphates and sodium can also manifest. One of the worst potential side effects is anaphylaxis, which is a massive drop in blood pressure due to arteries dilating excessively. This can then cause a large and potentially dangerous increase in heart rate. However, this is unlikely unless the supplement is taken is very extreme doses.
How to consume L-arginine + how much + side-effects
Arginine can be bought in powder as well as capsule form. Although powder is slightly cheaper, it is much less pleasant to consume due to it’s sulphuric smell caused by the sulfur group in the molecule. The recommended daily dosage of Arginine is 3,000mg (3g) per day. This quantity has been shown in several studies large enough to bring about the above health benefits. This quantity is also economical and easily measured by taking a certain number of capsules (4-6 depending on the capsule size) The consumption via capsules is therefore recommended.
There are also no side-effects to be expected under a dosage of 15g per day. If a man also takes the famous blue potency pill regularly however, he should first discuss taking Arginine with his doctor.
Consume or not Consume?
Of course, many companies are trying to capitalise on the health benefits of Arginine by selling supplements. In fact, this page’s editor believes that the health benefits are so great that Arginine should be consumed on a regular basis anyway. This will prevent heart disease, improve well-being and boost potency.
These should be researched thoroughly, because some products are expensive offering low nutrient dosages, whilst others are worth their while or exceptionally good.
Arginine is a very important micro nutrient (nutraceutical), which plays a vital role in a wide range of bodily processes. Despite it being produced naturally in the body, hundreds of studies produced over the space of decades have shown that supplementing the diet with arginine can have widespread health benefits.
Please discuss supplementing Arginine in detail with a fully qualified and registered professional such as your doctor or GP.
REFERENCED CLINICAL STUDIES:
- “Tapiero, H.; et al. (November 2002). “L-Arginine”. Biomedicine and Pharmacotherapy 56 (9): 439–445” ↩
- “Role of Arginine for Increasing Growth Hormone Levels” -http://personalfitnessresearch.com/l-arginine-boosts-hgh-growth-hormone-naturally-if-you-use-it-right” ↩
- “http://www.medscape.com/viewarticle/755625_2” ↩
- “http://www.ncbi.nlm.nih.gov/pubmed/12356784” ↩
- “http://www.ncbi.nlm.nih.gov/pubmed/20071141” ↩
- “http://www.apjcn.org/update%5Cpdf%5C0000%5C0%5C2617%5C2617–Online%20First.pdf” ↩
- “http://www.ncbi.nlm.nih.gov/pubmed/23554853” ↩
- “http://www.medscape.com/viewarticle/755625_2” ↩
- “Dong JY, Qin LQ, Zhang Z, Zhao Y, Wang J, Arigoni F, Zhang W. “Effect of oral L-arginine supplementation on blood pressure: a meta-analysis of randomized, double-blind, placebo-controlled trials.” American Heart Journal, 2011 Dec;162(6):959-65” ↩
- “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.” Journal of the British Association of Urological Surgeons, 1999 Feb;83(3):269-73” ↩
- “http://www.ncbi.nlm.nih.gov/pubmed/7701414” ↩
- “http://www.ncbi.nlm.nih.gov/pubmed/14515660” ↩
- “Imhof, Martin et al., “Improvement of sperm quality after micronutritient supplementation”, e-SPEN, the European e-Journal of Clinical nutrition and Metabolism” ↩
- “Sibal L, Agarwal SC, Home PD, Boger RH. “The Role of Asymmetric Dimethylarginine (ADMA) in Endothelial Dysfunction and Cardiovascular Disease.” Current Cardiology Reviews, 2010 May;6(2):82-90” ↩
- “Guthikonda S, Haynes WG. “Homocysteine: role and implications in atherosclerosis.” Current Atherosclerosis Reports” ↩
- “G. Leoncini*, R. Pascale, M. G. Signorello “Effects of homocysteine on l-arginine transport and nitric oxide formation in human platelets” European Journal of Clinical Investigation, Volume 33, Issue 8, pg 713-719” ↩
- “Thams P, Capito K. “L-arginine stimulation of glucose-induced insulin secretion through membrane depolarization and independent of nitric oxide.”, European Journal of Endocrinology, 1999 Jan;140(1)” ↩
- “L-arginine is essential for pancreatic beta-cell functional integrity, metabolism and defence from inflammatory challenge”, Journal of Endocrinology, 22 July 2011” ↩
- Smriga M, Ando T, Akutsu M, Furukawa Y, Miwa K, Morinaga Y “Oral treatment with L-lysine and L-arginine reduces anxiety and basal cortisol levels in healthy humans”. Institute of Life Sciences 28 (2): 85–90 ↩
- “Traditional Oven – L-lysine and L-arginine amino acid ratios in food iet. http://www.traditionaloven.com/tutorials/l-lysine_amino_acid.html” ↩
- “Arginine – Dosing, http://www.mayoclinic.com/health/l-arginine/NS_patient-arginine/DSECTION=dosing” ↩