Quick Comparison

Magnesium GlycinatePolygala Tenuifolia
Half-Life12-17 hours3-6 hours (tenuigenin and polygalasaponins)
Typical DosageStandard: 200-400 mg elemental magnesium daily (note: magnesium glycinate is ~14% elemental magnesium by weight, so 2000 mg magnesium glycinate provides ~280 mg elemental). Take in the evening for sleep benefits. Can be split into 2 doses.Standard: 100-300 mg extract daily (standardized to 3,6'-disinapoyl sucrose or polygalasaponins). Can be taken morning or evening. Some users take it before bed for dream enhancement. Effects noticeable within hours of first dose.
AdministrationOral (capsules, powder, tablets). Well-tolerated. Take with or without food.Oral (capsules, powder, tincture). Extract preferred over raw root for potency and reduced GI irritation.
Research Papers8 papers10 papers
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Mechanism of Action

Magnesium Glycinate

Magnesium is required for over 300 enzymatic reactions including neurotransmitter synthesis (tyrosine hydroxylase, tryptophan hydroxylase), energy production (ATPases, kinases, glycolytic enzymes), and DNA repair (PARP, DNA polymerases). In the brain, magnesium blocks NMDA receptors at the voltage-dependent Mg2+ binding site within the channel pore (GluN1/GluN2 subunits), preventing excessive calcium influx and excitotoxicity — Mg2+ is displaced only upon depolarization and glycine/glutamate binding. The glycine component activates inhibitory glycine receptors (GlyR alpha1/alpha2) in the brainstem and spinal cord, and serves as an obligatory co-agonist at the GluN1 glycine site of NMDA receptors. Glycine also modulates NMDA receptor function. Together, magnesium and glycine produce calming effects through complementary inhibitory mechanisms: reduced glutamatergic excitability and enhanced inhibitory neurotransmission.

Polygala Tenuifolia

The saponins (tenuigenin, polygalasaponins, onjisaponins) and oligosaccharide esters (3,6'-disinapoyl sucrose, tenuifolisides) have multiple neurological actions. They inhibit acetylcholinesterase (AChE) at the catalytic site, increasing synaptic acetylcholine and enhancing muscarinic M1/M4 and nicotinic receptor signaling. They promote BDNF and NGF expression via CREB and ERK/MAPK pathways, supporting neuroplasticity and neurogenesis in the hippocampus and subventricular zone. They modulate NMDA receptor function (possibly as positive allosteric modulators at the glycine site) and enhance long-term potentiation (LTP) via CaMKII and PKC. The anti-depressant effects involve monoaminergic modulation — increasing dopamine and norepinephrine via MAO inhibition or reuptake modulation — and HPA axis regulation (reducing CRH and cortisol). Tenuigenin may also activate TrkB receptors directly.

Risks & Safety

Magnesium Glycinate

Common

Mild drowsiness (often desired), loose stools at high doses (less than with other forms).

Serious

Avoid high doses with kidney impairment.

Rare

Diarrhea, nausea.

Polygala Tenuifolia

Common

Nausea, gastrointestinal irritation (take with food).

Serious

Limited long-term safety data in Western research.

Rare

Throat irritation, excessive salivation.

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