Arginine is the semi-essential amino acid that is the direct precursor of the nitric oxide (NO) — the most important signalling molecule in the cardiovascular system, the immune system, and the nervous system. The arginine is converted to the nitric oxide by the nitric oxide synthase (NOS) enzymes (endothelial NOS, eNOS; neuronal NOS, nNOS; inducible NOS, iNOS) — and this conversion is the primary mechanism by which the arginine supports the vasodilation, the immune function, and the neural signalling. The nitric oxide is one of the most important signalling molecules in the human body — it is involved in the regulation of the blood pressure (through the vasodilation of the blood vessels), the wound healing (through the activation of the immune cells and the fibroblasts), the erectile function (through the vasodilation of the corpus cavernosum), and the cognitive function (through the modulation of the neurotransmitter release and the synaptic plasticity). Without adequate arginine and nitric oxide synthesis, the blood vessels do not dilate properly, the blood pressure rises, the erectile function is impaired, and the immune function is compromised — the hallmark of the arginine deficiency and of the impaired nitric oxide production. The typical dietary arginine intake from the protein-rich foods (meat, fish, poultry, dairy, nuts, seeds) is 3-6g daily, and the therapeutic doses for the cardiovascular and immune support are 2-8g of the arginine supplement daily — making it one of the most evidence-based interventions for the cardiovascular health, the erectile dysfunction, and the immune support.
Arginine and the Cardiovascular Function
Arginine supports the cardiovascular function primarily through the production of the nitric oxide by the endothelial nitric oxide synthase (eNOS) — this enzyme converts the arginine to the nitric oxide in the endothelial cells that line the blood vessels, and the nitric oxide diffuses to the underlying vascular smooth muscle cells, where it activates the guanylyl cyclase and increases the cyclic GMP (cGMP) levels, causing the smooth muscle relaxation and the vasodilation. This vasodilation is the primary mechanism by which the nitric oxide regulates the blood pressure — the dilated blood vessels have a lower resistance to the blood flow, which reduces the systolic blood pressure and reduces the workload on the heart. The arginine also has other cardiovascular benefits — it reduces the platelet aggregation and the leukocyte adhesion (which are the key events in the initiation of the atherosclerosis), it reduces the vascular smooth muscle cell proliferation (which is the key event in the progression of the atherosclerosis and the restenosis), and it improves the insulin sensitivity (which is associated with the reduced cardiovascular risk). The arginine’s cardiovascular benefits are most pronounced in people with the endothelial dysfunction — which is the condition that is characterised by the impaired nitric oxide production and which is associated with the hypertension, the hypercholesterolaemia, the diabetes, the smoking, and the ageing. Without adequate arginine, the endothelial function is impaired, the blood vessels do not dilate properly, and the cardiovascular disease develops — the hallmark of the arginine deficiency and of the endothelial dysfunction.
The clinical importance of the arginine for the cardiovascular health is underscored by the observation that the arginine supplementation improves the endothelial function and reduces the blood pressure in people with the endothelial dysfunction and in the healthy older adults. A meta-analysis of 12 RCTs in over 500 participants with the hypertension found that the arginine supplementation at 2-6g daily significantly reduced the systolic blood pressure (by 5-10mmHg) and the diastolic blood pressure (by 3-5mmHg) — making arginine one of the most effective natural interventions for the hypertension. The arginine has also been shown to improve the erectile function in men with the mild to moderate erectile dysfunction (by 20-30%, as measured by the IIEF score), making it one of the most effective natural interventions for the ED.
Practical Application
For general arginine supplementation for the cardiovascular and immune support, the evidence-based approach is to supplement with 2-8g of L-arginine daily (as the pure L-arginine powder or capsule, taken in divided doses of 1-2g, 2-4 times per day). The arginine should be taken on the empty stomach (30-60 minutes before the meals or 2 hours after the meals) for the best absorption, and it should be taken with the vitamin C (which recycles the arginine and which protects the nitric oxide from the oxidative inactivation). The arginine is generally well-tolerated with no significant adverse effects at doses up to 10g daily, though it may cause the gastrointestinal symptoms (nausea, diarrhoea, abdominal pain) at the high doses, and it may interact with the antihypertensive drugs (because the combined effect on the blood pressure could be additive). For comprehensive cardiovascular and immune support, arginine pairs well with the citrulline (which is converted to the arginine in the kidneys and which has a longer half-life than the arginine, making it a more effective way to raise the arginine levels over time — the combination of the arginine and the citrulline is one of the most effective ways to increase the nitric oxide production and to support the cardiovascular health), with the antioxidants (vitamin C, vitamin E, polyphenols — which protect the nitric oxide from the oxidative inactivation and which work synergistically with the arginine for the endothelial function), with the omega-3 fatty acids (which have complementary effects on the endothelial function and on the inflammation), and with the exercise (which increases the eNOS activity and which works synergistically with the arginine for the nitric oxide production and for the cardiovascular adaptation).
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