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Supplement

L-arginine

An amino acid precursor of nitric oxide; for blood vessels it usually performs less well than citrulline (it is broken down in the gut).
Category
Scientific evidence
Low
Number of findings
1
Sources
Our own summaries · Cited studies
Recommended dose and how to use
3–6 g/day; higher doses for blood pressure/erection.

How to take it

3–6 g/day; higher doses for blood pressure/erection.

Safety

Digestive discomfort at high doses. Caution after a recent heart attack and with herpes (it may reactivate it).

Interactions

Do not combine with nitrates or with drugs for erectile dysfunction (hypotension).

Effect by goal · level of evidence

Lowering blood pressure

no clear effect Low meta-analysis (AAA)

No clear effect on blood pressure — null/mixed result

View the study (meta-analysis) →

In depth

⏱ 3 min read

L-arginine is a conditionally essential amino acid that the body synthesizes endogenously in adequate amounts during normal adult life, but whose requirements increase during growth, tissue injury, severe infection, and significant metabolic stress; its pharmacological importance as a supplement stems from a very specific biochemical role: it is the exclusive substrate of the enzyme nitric oxide synthase (NOS), which produces nitric oxide (NO), an essential mediator of vasodilation, neuromuscular signaling, immune function, and blood pressure regulation; drug therapies that increase endogenous NO (nitroglycerin, sildenafil, others) are established clinical tools, and nutritional modulation of the NO pathway's substrate with L-arginine has a reasonable mechanistic basis, although clinical results are heterogeneous.

Erectile function and mild erectile dysfunction

In mild to moderate erectile dysfunction, several small trials have documented significant improvements with high doses of L-arginine (5 g/day for several weeks), an indication consistent with the role of NO in the vasodilation of the corpus cavernosum needed for an erection; the effect sizes are quantitatively smaller than those of PDE-5 inhibitors (sildenafil, tadalafil), but it may have a place as a first-line option in very mild dysfunction or as an adjunct; combining it with pycnogenol enhances the effect in some studies.

Endothelial function and cardiovascular disease

In people with documented endothelial dysfunction (an early factor common to multiple cardiovascular diseases), several trials have shown acute and chronic improvements in endothelial function with supplementation at 3-9 g/day for weeks to months; effects on hard cardiovascular events are less clear, and a trial in patients with a recent heart attack (VINTAGE MI) showed a neutral or unfavorable result, which considerably qualifies its use in cardiovascular secondary prevention.

Hypertension and blood pressure

In mild arterial hypertension, several small studies have documented modest blood pressure reductions with supplementation at 6-9 g/day for weeks to months, an indication consistent with the NO-dependent mechanism but with smaller effect sizes than those of specific pharmacological antihypertensives.

Athletic performance and pre-workout vasodilation

In the fitness world, L-arginine has been marketed for decades as a “pre-workout” to improve vasodilation, the muscle “pump,” and performance; the rigorous clinical data are disappointing: oral L-arginine has limited bioavailability and rapid hepatic hydrolysis, which significantly reduces its real capacity to raise plasma NO concentrations; citrulline (a precursor that bypasses hepatic metabolism and is converted to arginine in the kidney) is pharmacologically more efficient for this specific indication.

How to take it and precautions

The doses studied range from 3 to 9 grams per day, divided into 2-3 doses on an empty stomach to optimize absorption; typical commercial products are powder or capsules; the powder has a characteristic bitter taste that is hard to mask; the effects on endothelial function and vasodilation are acute at high doses but the duration of the effect is limited; very high doses cause digestive discomfort that limits practical usefulness.

Generally well tolerated at moderate doses; the most common adverse effects are digestive discomfort (nausea, diarrhea, abdominal cramps at high doses), which considerably limits practical dosing; the most important clinical consideration is activation of the herpes simplex virus (arginine favors viral replication, and the imbalance with lysine can precipitate outbreaks in predisposed people): people with recurrent oral or genital herpes should avoid high doses of arginine or, if they take them, combine it with supplemental lysine; people with a recent myocardial infarction should avoid L-arginine because of the unfavorable data from the VINTAGE MI trial; those taking pharmacological nitrates (nitroglycerin, isosorbide) or PDE-5 inhibitors (sildenafil) may experience a potentiated hypotensive effect with a risk of syncope; in pregnancy and breastfeeding, specific data as a supplement are limited; citrulline products offer a better pharmacokinetic profile for most of the indications for which arginine has traditionally been used.

References

  1. Chen, J. et al. (1999). 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 83, 3. doi:10.1046/j.1464-410x.1999.00041.x
  2. Schulman, S.P. et al. (2006). L-arginine therapy in acute myocardial infarction: the Vascular Interaction with Age in Myocardial Infarction (VINTAGE MI) randomized clinical trial. JAMA 295, 1. doi:10.1001/jama.295.1.58
  3. Dong, J.Y. et al. (2011). Effect of oral l-arginine supplementation on blood pressure: a meta-analysis of randomized, double-blind, placebo-controlled trials. Am Heart J 162, 6. doi:10.1016/j.ahj.2011.09.012
  4. Stanislavov, R.; Nikolova, V. (2003). Treatment of erectile dysfunction with pycnogenol and L-arginine. J Sex Marital Ther 29, 3. doi:10.1080/00926230390155104
  5. Bahadoran, Z.; Mirmiran, P.; Ghasemi, A. (2018). Role of nitric oxide in insulin secretion and glucose metabolism. Trends Endocrinol Metab 29, 2. doi:10.1016/j.tem.2017.12.001

Information, not medical advice. Scientific evidence reflects the quality of the studies.

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