Quick Comparison
| Agmatine Sulfate | NMN (Nicotinamide Mononucleotide) | |
|---|---|---|
| Half-Life | 2-3 hours | 2-3 minutes in blood (rapidly converted to NAD+). NAD+ half-life: 1-2 hours in tissue |
| 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: 250-1000 mg daily. Sublingual may improve bioavailability by bypassing first-pass metabolism. Take in the morning — NAD+ follows circadian rhythm and morning supplementation aligns with natural peaks. Effects build over weeks. |
| Administration | Oral (powder, capsules). Take on empty stomach for best absorption. | Oral (capsules, powder, sublingual). Sublingual may improve bioavailability. Store in cool, dry place. |
| Research Papers | 10 papers | 10 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.
NMN (Nicotinamide Mononucleotide)
NMN is transported into cells via the Slc12a8 transporter (highly expressed in the small intestine and brain) and converted to NAD+ by nicotinamide mononucleotide adenylyltransferases (NMNAT1 in the nucleus, NMNAT2 in axons/Golgi, NMNAT3 in mitochondria). Elevated NAD+ activates the sirtuin family of NAD+-dependent protein deacetylases: SIRT1 deacetylates PGC-1alpha to promote mitochondrial biogenesis, SIRT3 activates superoxide dismutase 2 (SOD2) and isocitrate dehydrogenase 2 (IDH2) for mitochondrial antioxidant defense, and SIRT6 promotes base excision repair of oxidative DNA damage. NAD+ is also consumed by poly(ADP-ribose) polymerases (PARP1/2) during DNA repair — age-related NAD+ depletion impairs PARP function, allowing DNA damage accumulation. In neurons, NAD+ is required for glycolysis (GAPDH cofactor), the TCA cycle, and Complex I of the electron transport chain, directly fueling the enormous ATP demands of synaptic transmission. NAD+ decline with aging (approximately 50% reduction between ages 40-60) reduces all of these processes simultaneously, creating a cascade of mitochondrial dysfunction, impaired DNA repair, and neuroinflammation that NMN supplementation aims to reverse.
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.
NMN (Nicotinamide Mononucleotide)
Common
Mild flushing, nausea, headache initially.
Serious
Long-term human safety data still limited (first human trials completed 2020-2023). Theoretical concern about promoting cancer growth in existing tumors (NAD+ fuels fast-growing cells).
Rare
Insomnia if taken late.
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.
NMN (Nicotinamide Mononucleotide) →
A direct precursor to NAD+ (nicotinamide adenine dinucleotide), a coenzyme essential for cellular energy production, DNA repair, and sirtuin activation. NAD+ levels decline 50% between ages 40 and 60, contributing to age-related cognitive decline and neurodegeneration. NMN supplementation restores NAD+ levels and improves mitochondrial function, memory, and neuroplasticity in animal models.