What are the health benefits of arginine supplementation?

Health Benefits of Arginine Supplementation

Arginine supplementation offers limited proven health benefits, with the strongest evidence supporting its use for improving pulmonary hemodynamics in pulmonary arterial hypertension patients and potentially preventing necrotizing enterocolitis in preterm infants.

Cardiovascular Benefits

Pulmonary Arterial Hypertension

Arginine has shown promising effects in patients with pulmonary arterial hypertension (PAH):

• Oral L-arginine supplementation (0.5 g/10 kg body weight) demonstrated a 9% decrease in mean pulmonary arterial pressure and a 16% decrease in pulmonary vascular resistance 1
• One-week supplementation resulted in slight increases in peak oxygen uptake and significant decreases in ventilatory response to carbon dioxide production 1
• The mechanism involves increased nitric oxide production, as evidenced by increased plasma L-citrulline levels 1

However, long-term benefits remain uncertain, as rigorous randomized multicenter trials of long-term oral arginine supplementation in PAH patients are lacking 1.

Blood Pressure and Vascular Compliance

In individuals with borderline or frank hypertension:

• Sustained-release L-arginine (2.1 g daily) for one week reduced systolic blood pressure by approximately 11 mm Hg in hypertensive individuals 2
• Significant improvements in large artery compliance (23% improvement) were observed 2

Sepsis and Critical Illness

Despite theoretical benefits, clinical evidence does not support arginine supplementation in sepsis:

• Current guidelines suggest against using arginine to treat sepsis and septic shock (weak recommendation, low quality of evidence) 1
• Arginine availability is reduced in sepsis, potentially leading to reduced nitric oxide synthesis and microcirculatory dysfunction 1
• However, arginine supplementation may cause unwanted vasodilation and hypotension in septic patients 1
• Clinical trials have shown variable effects on mortality, with some suggesting possible harm in septic patients 1

Erectile Dysfunction

L-arginine serves as a substrate for nitric oxide synthesis, which is crucial for penile erection:

• L-citrulline supplementation (1.5 g/day for one month), which converts to L-arginine, improved erection hardness in 50% of men with mild erectile dysfunction 3
• This approach may be particularly useful for patients with psychological fear of phosphodiesterase type-5 inhibitors 3

Neonatal Applications

Arginine supplementation shows promise in preventing necrotizing enterocolitis (NEC) in preterm infants:

• A double-blind RCT in 152 premature infants found that L-arginine supplementation resulted in a significant decrease in NEC incidence 1
• Current guidelines conditionally recommend arginine supplementation for NEC prevention in preterm infants 1

Peripheral Arterial Disease

Evidence for arginine in peripheral arterial disease is limited:

• One placebo-controlled trial found that intravenous L-arginine (8 g twice daily) improved pain-free and maximal walking distance after 3 weeks 1
• Another study using a food bar containing 3.3 g of L-arginine showed modest improvement in walking distance after 2 weeks 1
• However, a larger placebo-controlled trial yielded negative results 1

Safety Considerations

• The observed safe level for oral administration of arginine is approximately 20 g/day 4
• Higher levels have been tested in short-term studies without serious adverse effects 4
• Arginine has been used safely in vulnerable populations including pregnant women and preterm infants 4

Clinical Application Guidance

When considering arginine supplementation:

1. For PAH patients: Consider oral supplementation at 0.5 g/10 kg body weight, but recognize that long-term benefits remain unproven
2. For mild erectile dysfunction: Consider L-citrulline (1.5 g/day) as a potentially safer alternative to direct arginine supplementation
3. For preterm infants at risk of NEC: Consider arginine supplementation following pediatric guidelines
4. Avoid in sepsis and septic shock: Due to potential for unwanted vasodilation and hypotension

Potential Pitfalls

• Excessive arginine supplementation may increase polyamines, which are proproliferative and could have unintended consequences 1
• Benefits observed in short-term studies may not translate to long-term improvements 1
• Arginine supplementation in sepsis could worsen hypotension and potentially harm patients 1

While arginine plays important roles in nitric oxide synthesis, vascular function, and immune regulation, the clinical evidence supporting widespread supplementation remains limited to specific conditions.