L-Citrulline vs L-Theanine

Mechanism

L-Citrulline is converted to L-arginine in the kidneys via argininosuccinate synthase and argininosuccinate lyase (bypassing hepatic first-pass metabolism that degrades oral L-arginine). L-arginine is then the substrate for endothelial nitric oxide synthase (eNOS), producing nitric oxide (NO). NO activates soluble guanylyl cyclase (sGC), increasing cGMP, causing vascular smooth muscle relaxation and vasodilation. Citrulline also participates in the urea cycle (ammonia detoxification), and supplementation increases plasma arginine more effectively than arginine supplementation itself due to bypass of intestinal and hepatic arginase.

Standard Dosing

3-6g L-citrulline daily or 6-8g citrulline malate

Timing

30-60 minutes pre-workout for exercise performance. For blood pressure: split AM/PM doses. Powder form in water.

Cycle Duration

ongoing

Side Effects

• Mild GI discomfort
• Bloating
• Headache (vasodilation)
• Generally very well-tolerated even at high doses

Contraindications

• Concurrent nitroglycerin/nitrate therapy
• Severe hypotension
• Urea cycle disorders (citrullinemia)

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Mechanism

L-Theanine (gamma-glutamylethylamide) crosses the blood-brain barrier via the large neutral amino acid transporter. It increases alpha brain wave activity (8-13 Hz, associated with relaxed alertness), enhances GABA, serotonin, and dopamine levels in the brain, and antagonizes glutamate excitotoxicity by blocking glutamate binding at AMPA, kainate, and NMDA receptors. It also increases BDNF and NGF expression, supporting neuroplasticity. The combination of glutamate antagonism and GABA/serotonin enhancement produces anxiolysis without sedation — a 'calm focus' state.

Standard Dosing

100-200mg daily (or as needed for acute anxiety/focus)

Timing

Flexible: morning for calm focus (stack with caffeine), before stressful events, or evening for relaxation/sleep onset. Onset: 30-60 minutes oral, 15-20 min sublingual.

Cycle Duration

ongoing or as needed

Side Effects

• Headache (rare)
• GI discomfort (rare)
• Dizziness at very high doses
• Generally extremely well-tolerated

Contraindications

• Very few — one of the safest supplements available. Caution in severe hypotension.

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