Table of Contents
L-Arginine is a semi-essential amino acid that is known as the precursor for the endogenous synthesis of nitric oxide (NO) [1; 2], and is known to possess strong immune modulation properties . Food rich in L-Arginine include seafood, watermelon juice, nuts, seeds, algae, meats, along with concentrate isolates of rice and soy protein . As L-Arginine (Figure 1) is a precursor of NO, it has been known to have a key role in endothelium-dependent vasodilation .
Mechanisms of action
L-Arginine, as a semi-essential amino acid, becomes an essential amino acid under certain circumstances , such as catabolic stress, infant growth, along with problems associated with the intestinal system and kidneys . In addition, L-Arginine is required in order for the body to synthesise creatine and agmatine . One mechanism L-Arginine contributes to is the removal of excess ammonia from the body, including the formation of muscle protein, amino acids and creatine . ~40% of dietary L-arginine is broken down by the intestine before entering the circulation  – Figure 2.
Benefits of L-Arginine
Acute and chronic administration of L-Arginine, investigating in vivo studies, has shown that this amino acid improves vascular responsiveness . L-arginine not only is a precursor for NO, with its role in protein synthesis; but, L-arginine is also a precursor to around six important compounds . L-arginine is able to modulate and influence the biochemical functions of cells, is a substrate for protein synthesis and can be mobilised for a vast variety of metabolic pathways in the body . Benefits of L-arginine supplementation and intake include assisting the immune system, wound healing, vascular tone, insulin sensitivity and endothelial function .
L-arginine and weight loss
Fat oxidation and a tissue-specific reduction of fat synthesis is a key feature of L-arginine and nitric oxide (NO) . L-arginine has been investigated for its role in increasing muscle gain, whilst simultaneously reducing fat deposition . Supplementing animals with L-arginine over a 60-day period showed a decrease in in body fat growth in growing pigs . Authors of these results reported the novelty in using L-arginine in treating obesity in humans. Another study documented L-arginine’s effect on a diet-induced obesity rat model . This work adequately described that 12-weeks treatment of rats with L-arginine showed a reduction in relative weights of white fat pads by 30% .
L-arginine and blood pressure
Studies on the effect of L-arginine on blood pressure have revealed that this amino acid provides a lowering of blood pressure . An L-arginine enriched diet, using both natural foods or pharmacologic preparation, was administered to six healthy individuals, and results showed that L-arginine was able to decrease blood pressure in the subjects . In other work, L-arginine was assessed for its role in influencing blood pressure in heart failure (HF) patients with preserved ejection fraction (HFpEF) . This work was able to show that L-arginine could improve pulmonary artery pressure and right ventricular ejection fraction after 2-months L-arginine treatment . This study of L-arginine translates to its potential in preventing endothelial dysfunction  – Figure 3.
Comparatively, L-arginine in its effect on insulin sensitivity in obese individuals showed a lowering of systolic and diastolic blood pressure after administration of 8.3g/day of L-arginine over 21 days . Moreover, a 30g intravenously administered dose of L-arginine in 8 healthy male patients lowered blood pressure at time-dependent points  – Figure 4.
L-Arginine helps enhance circulation to the reproductive organs, and might help in oocyte development . In one study assessing nutritional supplements in optimising reproductive health in women, an L-Arginine extract was found after three months to increase mean midluteal phase progesterone levels . Additionally, after five months treatment, five out of 15 female participants were pregnant, compared with none in the placebo group  The authors noted no adverse side effects from the 3-capsules per day.
Nitric Oxide (NO) is suggested to be a key noncholinergic neurotransmitter and chemical mediator of erectile dysfunction . A double-blind placebo-controlled study assessing a high-dose (5g/day) L-arginine on men with erectile dysfunction showed significant subjective improvements in sexual function . For women, L-Arginine combined with alpha2-blocker yohimbine was used to assess its effects on improving sexual arousal in postmenopausal women with Female Sexual Arousal Disorder . Remarkably, results showed that the combination of L-Arginine – at a 6g dose – increased vaginal pulse amplitude responses compared with placebo . Another similar study, using a randomised clinical trial setting, was conducted evaluating efficacy and safety of 6g L-arginine glutamate for treatment of erectile dysfunction (ED) . L-arginine doses were administered orally 1-2 hours before sexual intercourse; results showed a positive improvement in improving erectile dysfunction (ED) in patients with mild to moderate ED .
L-arginine and pregnancy
L-arginine has been used as a supplement for assessing its role in pregnant women . L-arginine was hypothesised to be implicated in the development of pre-eclampsia. In a study seeking to determine the effects of an L-arginine supplementation, 228 women were administered L-arginine and results were positive in showing that L-arginine reduced incidences of pre-eclampsia in a high-risk population . Additionally, L-arginine was studied to measure its effectiveness in reproductive performance in pregnant pigs . L-arginine, being a key in animal metabolism – exclusively as a precursor for nitric oxide (NO) – has as role in enhancing blood flow during ovine pregnancy. Results showed that L-arginine supplementation was able to increase the number of pigs born alive and healthy by 22% .
L-arginine body building and exercise
Although limited research has been carried out how L-arginine improves muscle performance, reports have documented the role L-arginine plays in maximal strength , and exercise performance. In one study, in conjunction with assessing the combined effects with creatine, L-arginine along with creatine improved the number of repetitions performed on a bench press exercise . Remarkably, 10 days of L-arginine supplementation improved peak power on a routine Wingate cycling test. Conclusions drawn from this study revealed that an L-arginine supplement has an advantage over creatine alone. Interestingly, L-arginine has been investigated for its effects on physiological and metabolic changes during exercise . In 8 healthy patients, L-arginine significantly decreased exercise-induced peak plasma ammonia and lactate . The relevance of a plasma build-up of ammonia and lactate during physical exercise is significantly related to muscle fatigue; and, L-arginine was shown to alleviate this stress during exercise .
L-arginine and sleep
Nitric Oxide (NO) has a role in obstructive sleep apnoea (OSA) [24; 25]. Plasma levels of L-arginine have been suggested to increase after a single night of continuous positive airway pressure (CPAP) therapy in patients with sleep apnoea . One interesting study looked at overnight plasma NO levels in sleep apnoea patients and how treatment with nasal continuous positive airway pressure (nCPAP) affected the day after L-arginine levels . After treatment, all patients were recorded as having significant increases of L-arginine. Remarkably, results suggested the importance of Nitric oxide (NO) in sleep apnoea .
Side-effects of L-arginine
L-arginine is utilised since it has a pivotal role in making urea, NO and creatine ; and so, L-arginine has great utility in treating problems related to the urea cycle. Problems with L-arginine consumption have been associated with gastrointestinal toxicity . Side effects vary from nausea and diarrhea – from single large doses of L-arginine -, to no side effects at all [26; 2]. As studies assessing the effectiveness of L-arginine differ; dosage regime could play a major role in whether adverse effects are recognised. High doses of L-arginine – 30g – have reported hypertension with tachycardia, along with an increase in cardiac output . In addition, anaphylaxis might also be a side effect from L-arginine supplementation; in this regard, those taking L-arginine should reconsider if suffering from allergic tendencies . In patients suffering from lover and kidney failure, IV administration of L-arginine was reported to cause heightened Potassium blood levels (hyperkalaemia) and hyperphosphataemia, which is an abnormally high level of phosphate in blood.
Shao and Hathcock (2008) summarised L-arginine according to the following criteria:
- No human clinical trials of L-arginine found any ‘No observed adverse effect level’ (NOAEL).
- Observed Safe Level (OSL) of L-arginine (summarised in Table 1):
|L-arginine dose||OSL rating|
|42 g/day||Does not pass OSL|
|30 g/day||Does not pass OSL|
|24.8 g/day||Does not pass OSL|
|21 g/day||Does not pass OSL|
|20 g/day|| |
Safe for use with no adverse effects reported under documented dosage per study.
Table 1. The Observed Safe Level (OSL) was adopted in 2006 (originally named Highest Observed Intake (HOI) by the FAO/WHO 2006 report.
Literature has described 3-6 grams L-arginine to be a safe dose, with this dose schedule rarely showing side effects . However, the majority of side effects from L-arginine have been reported at doses exceeding 9 grams – when taken as part of daily dose regime of >30d per day L-arginine . According to the observed safe level (OSL) of L-arginine, evidence indicates that adverse effects are absent of up to 20 grams per day L-arginine – considered normal in healthy adults . Highest L-arginine dose recorded was 42g/day for 6 weeks in patients suffering from cystic fibrosis, with no adverse effects reported . Table 2 describes some L-arginine doses relative to individual studies.