Arginine is a semi-essential amino acid that is one of the most important regulators of the vascular tone — it is the direct precursor of the nitric oxide (NO) through the nitric oxide synthase (NOS) enzyme pathway, and it is therefore essential for the regulation of the blood vessel tone, the blood flow, the blood pressure, and the delivery of the oxygen and the nutrients to the working muscles and the vital organs. The nitric oxide is synthesised from the arginine by the three nitric oxide synthase isoforms (endothelial NOS or eNOS, neuronal NOS or nNOS, and inducible NOS or iNOS), and each isoform produces NO in different physiological contexts — the eNOS-derived NO regulates the basal vascular tone and the blood flow, the nNOS-derived NO acts as a neurotransmitter in the brain and the peripheral nervous system, and the iNOS-derived NO is produced in immune cells during the inflammatory response. The arginine-NO pathway is the primary mechanism by which the body regulates the vascular tone and the blood pressure, and the dysfunction of this pathway (due to the asymmetric dimethylarginine or ADMA accumulation, the eNOS uncoupling, or the oxidative stress) is one of the most important contributors to the endothelial dysfunction, the hypertension, and the cardiovascular disease. Without adequate arginine and NO synthesis, the blood vessels cannot relax properly, the blood flow is impaired, and the blood pressure rises — the hallmark of the arginine deficiency and of the endothelial dysfunction states that are associated with the cardiovascular disease, the metabolic syndrome, and the normal biological ageing.
Arginine and the Exercise Performance
Arginine supports the exercise performance primarily through its role as the precursor of the NO that regulates the blood flow and the oxygen delivery to the working muscles — the increased NO production during the exercise causes the vasodilation of the skeletal muscle blood vessels, which increases the blood flow, the oxygen delivery, and the nutrient delivery to the active muscle fibres, thereby delaying the fatigue and improving the exercise performance. The arginine supplementation (at doses of 3-6g, taken 30-60 minutes before the exercise) has been shown to increase the plasma arginine levels by 30-50% and to increase the NO production (as measured by the plasma nitrite levels) by 20-40% — with concurrent improvements in the exercise performance (as measured by the time to exhaustion and the VO2max). The arginine is particularly effective for the high-intensity exercise and for the endurance exercise, where the increased oxygen delivery to the working muscles is the primary determinant of the performance.
The clinical importance of the arginine for the cardiovascular health and for the exercise performance is underscored by the observation that the arginine supplementation improves the endothelial function and reduces the blood pressure in people with hypertension and with the endothelial dysfunction. A meta-analysis of 9 RCTs in over 500 patients with hypertension found that the arginine supplementation at 4-6g daily significantly reduced the systolic blood pressure (by 5-8 mmHg), reduced the diastolic blood pressure (by 3-5 mmHg), and improved the endothelial function (as measured by the flow-mediated dilation of the brachial artery) — demonstrating the potent and clinically meaningful cardiovascular effect of the arginine in people with elevated blood pressure.
Practical Application
For general arginine support for the cardiovascular health and for the exercise performance, the evidence-based approach is to supplement with the L-arginine at 3-6g daily (as the pure arginine powder or capsules, taken in divided doses of 1-2g). The arginine should be taken on an empty stomach (30-60 minutes before the meals or the exercise) for the best absorption and for the maximum NO production effect. The arginine is generally well-tolerated with no significant adverse effects at the doses that are used for the cardiovascular support (up to 10g daily), though some people may experience mild gastrointestinal discomfort or the flushing at the higher doses. For comprehensive arginine support and cardiovascular protection, arginine pairs well with the citrulline (which is converted to arginine in the body and which provides a more sustained increase in the arginine levels than the direct arginine supplementation — the combination of the citrulline and the arginine is one of the most effective and most evidence-based combinations for the NO production and for the cardiovascular protection, and it is significantly more effective than either compound alone for the increase of the arginine levels and for the NO production), with the glycine (which is an inhibitory neurotransmitter that works synergistically with the arginine for the relaxation and for the stress reduction — the combination of the arginine and the glycine is one of the most effective combinations for the natural relaxation and for the stress management, and it is particularly useful for people with high stress or with the anxiety that is associated with the elevated blood pressure), and with the omega-3 fatty acids (which have complementary anti-inflammatory and endothelial-protective effects on the cardiovascular system — the combination of the arginine and the omega-3 fatty acids is one of the most effective combinations for the comprehensive cardiovascular protection and for the reduction of the cardiovascular disease risk).
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