Quick Comparison
| Agmatine Sulfate | Gotu Kola | |
|---|---|---|
| Half-Life | 2-3 hours | 2-4 hours (asiaticoside, madecassoside) |
| Typical Dosage | Standard: 500-2000 mg daily in 1-3 doses. For mood: 1000-2000 mg. For pain: 1000-2500 mg. Take on empty stomach. Agmatine sulfate is the most common supplement form. May enhance the effects of some nootropics and medications — research interactions. | Standard: 500-1000 mg standardized extract daily (triterpenes: asiaticoside, madecassoside). Traditional dose: 1-2 grams dried herb as tea. ECa 233 is a well-studied standardized extract. Can be taken morning or evening — mild enough for bedtime use. |
| Administration | Oral (powder, capsules). Take on empty stomach for best absorption. | Oral (capsules, extract, tea, tincture). ECa 233 standardized extract for consistent dosing. |
| Research Papers | 10 papers | 9 papers |
| Categories |
Mechanism of Action
Agmatine Sulfate
Agmatine is a polyamine neuromodulator with multiple targets: (1) NMDA receptor antagonist at the polyamine binding site (GluN1/GluN2B) — reduces excitotoxicity, pain signaling, and blocks the receptor's open channel. (2) Imidazoline I1 and I2 receptor agonist — I1 in the rostral ventrolateral medulla reduces sympathetic tone; I2 modulates monoamine oxidase and provides anxiolytic/antidepressant effects. (3) Selective nNOS (neuronal nitric oxide synthase) inhibitor — reduces peroxynitrite formation and oxidative stress while preserving eNOS (endothelial) function for vascular health. (4) Alpha-2 adrenergic receptor agonist — reduces norepinephrine release from locus coeruleus, promoting calm. (5) Modulates opioid receptors — enhances mu-opioid analgesia, potentiates delta-opioid, and may reduce tolerance via nitric oxide and NMDA mechanisms.
Gotu Kola
Triterpene saponins (asiaticoside, madecassoside, asiatic acid, madecassic acid) are the primary bioactives. They increase BDNF expression in the hippocampus via CREB and ERK/MAPK pathways, promoting neuroplasticity, synaptogenesis, and memory formation. They enhance collagen type I synthesis through stimulation of fibroblasts and improve microcirculation via VEGF and angiopoietin modulation. Anxiolytic effects occur through positive allosteric modulation of GABA-A receptors (possibly at the benzodiazepine or neurosteroid site) and reduction of acoustic startle response (amygdala modulation). Gotu kola inhibits acetylcholinesterase (AChE), mildly increasing synaptic acetylcholine. Anti-inflammatory effects come from NF-kB inhibition (IkB stabilization) and TNF-alpha suppression. Asiatic acid may also activate PPAR-gamma.
Risks & Safety
Agmatine Sulfate
Common
Mild gastrointestinal discomfort, diarrhea at high doses.
Serious
May potentiate opioid medications (increased sedation risk). May lower blood pressure.
Rare
Headache, nausea.
Gotu Kola
Common
Very well-tolerated. Mild GI upset, drowsiness.
Serious
Rare hepatotoxicity reported — avoid with liver disease and limit use to 6-week cycles.
Rare
Headache, dizziness, skin sensitivity to sunlight.
Full Profiles
Agmatine Sulfate →
A metabolite of L-arginine produced by decarboxylation. Agmatine is an endogenous neuromodulator that acts on multiple receptor systems — it blocks NMDA receptors, activates imidazoline receptors, inhibits nitric oxide synthase, and modulates opioid signaling. This makes it useful for neuropathic pain, mood, stress resilience, and as a complement to other nootropics. Also enhances insulin sensitivity and nitric oxide production.
Gotu Kola →
Centella asiatica is an Ayurvedic and Chinese medicine herb known as the 'herb of longevity.' It has been used for centuries to enhance memory, promote wound healing, and reduce anxiety. Modern research confirms it increases BDNF, enhances collagen synthesis, improves microcirculation, and has anxiolytic effects. Unlike most adaptogens, gotu kola has clinical evidence for improving memory and attention in healthy adults.